Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.     

Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.     

Human cardiovascular reactions to simulated hypovolaemia, modified by the opiate antagonist naloxone

Six healthy males were exposed to 20 mm Hg lower body negative pressure (LBNP) for 8 min followed by 40 mm Hg LBNP for 8 min. Naloxone (0.1 mg.kg-1) was injected intravenously during a 1 h resting period after which the LBNP protocol was repeated. Systolic, mean, and diastolic arterial blood pressures (SAP, MAP, DAP), and central venous pressure (CVP) were obtained using indwelling catheters. Cardiac output (CO), forearm blood flow (FBF), heart rate (HR), left ventricular ejection time (LVET), and electromechanical systole (EMS) were measured non-invasively. Pulse pressure (PP), stroke volume (SV), total peripheral resistance (TPR), forearm vascular resistance (FVR), systolic ejection rate (SER), pre-ejection period (PEP), PEP/LVET and indices for the systolic time intervals (LVETI, EMSI, PEPI) were calculated. During the second LBNP exposure, only two parameters differed from the pre-injection values: DAP at LBNP = 40 mm Hg increased from 60.0 +/- 4.8 mm Hg to 64.8 +/- 4.1 mm Hg (N = 4, p less than 0.02) and LVETI at LBNP = 20 mm Hg increased from 384.4 +/- 5.2 ms to 396.8 +/- 6.2 ms (N = 6, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Voltage-sensitive dye mapping in Langendorff-perfused rat hearts

An imaging system suitable for recordings from Langendorff-perfused rat hearts using the voltage-sensitive dye 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) has been developed. Conduction velocity was measured under hyper- and hypokalemic conditions, as well as at physiological and reduced temperature. Elevation of extracellular [K(+)] to 9 mM from 5.9 mM caused a slowing of conduction velocity from 0.66 +/- 0.08 to 0.43 +/- 0.07 mm/ms (35%), and reduction of the temperature to 32 degrees C from 37 degrees C caused a slowing from 0.64 +/- 0.07 to 0.46 +/- 0.05 mm/ms (28%). Ventricular activation patterns in sinus rhythm showed areas of early activation (breakthrough) in both the right and left ventricle, with breakthrough at a site near the apex of the right ventricle usually occurring first. The effects of mechanically immobilizing the preparation to reduce motion artifact were also characterized. Activation patterns in epicardially paced rhythm were insensitive to this procedure over the range of applied force tested. In sinus rhythm, however, a relatively large immobilizing force caused prolonged PQ intervals as well as altered ventricular activation patterns. The time-dependent effects of the dye on the rat heart were characterized and include 1) a transient vasodilation at the onset of dye perfusion and 2) a long-lasting prolongation of the PQ interval of the electrocardiogram, frequently resulting in brief episodes of atrioventricular block.     

Anacrotic "notch" on the upstroke of external carotid curve may indicate a critically high systolic pulmonary arterial pressure value.

Acute respiratory failure is followed by decreased left ventricular performance probably due to the right ventricle dilatation induced by pulmonary hypertension and intraventricular septal shift to the left. An anacrotic notch on the upstroke slope of the carotid curve was detected in 22 of 36 hemodynamic studies with simultaneous ECG, PCG and external pulse carotid curve recording in 7 burned patients with acute respiratory failure. Comparing the values (x +/- SEM) obtained in group with notch and in group without notch, PAPs, PAPm, PVRI were higher (56 +/- 2.30 mmHg; 32 +/- 0.99 mm Hg; 543 +/- 56.8 dyn x s/cm5/m2 versus 32 +/- 1.08 mm Hg; 20 +/- 0.9 mm Hg; 173 +/- 14.7 dyn x s/cm5/m2) and CI and LVSWI were lower (2.6 +/- 0.17 l/min/m2; 25.8 +/- 2.41 g x m/m2; versus 3.8 +/- 0.26 l/min/m2; 38.3 +/- 2.82 g x m/m2) in group with notch. As it is shown by 11 paired measurements where the notch disappeared immediately after starting vasodilator therapy PAPs, PAPm, PVRI decreased (from 54 +/- 3.1, 35 +/- 0.8 mm Hg, 498 +/- 64.1 dyn x s/cm5/m2 to 35 +/- 0.8, 21 +/- 1.1 mmHg, 189 +/- 18.4 dyn x s/cm5/m2 respectively) and heart performance improved. Since the left ventricle contractility (characterized by EF, PCWP, ICT) was normal in both groups, our findings suggest that critically high PAPs values (over 40 mmHg) cause a septal bulging at the beginning of the systole which in turn narrows the left ventricle outflow tract. Regarding to the clinical importance of the deteriorated biventricular function at the critically high PAPs evidenced by notch phenomenon on carotid curve but measurable only by indwelling pulmonary arterial catheterization always being a source of infection, the noninvasive parameters as independent variables were entered into canonical discriminant analysis. The ratio of the correctly classified cases was 89%.     

Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure

The peptide urotensin-II (U-II) has been described as most potent vasoconstrictor identified so far, but plasma values in humans and its role in cardiovascular pathophysiology are unknown. We investigated circulating urotensin-II and its potential role in human congestive heart failure (CHF). We enrolled control individuals (n=13; cardiac index [CI], 3.5+/-0.1 l/min/m2; pulmonary wedge pressure [PCWP], 10+/-1 mm Hg), patients with moderate (n=10; CI, 2.9+/-0.3 l/min/m2; PCWP, 14+/-2 mm Hg) and severe CHF (n=11; CI, 1.8+/-0.2 l/min/m2; PCWP, 33+/-2 mm Hg). Plasma levels of urotensin-II differed neither between controls, patients with moderate and severe CHF nor between different sites of measurement (pulmonary artery, left ventricle, coronary sinus, antecubital vein) within the single groups. Hemodynamic improvement by vasodilator therapy in severe CHF (CI, +78+/-3%; PCWP, -55+/-3%) did not affect circulating U-II over 24 h. Preprourotensin-II mRNA expression in right atria, left ventricles, mammary arteries and saphenous veins did not differ between controls with normal heart function and patients with end-stage CHF. In conclusion, urotensin-II plasma levels and its myocardial and vascular gene expression are unchanged in human CHF. Circulating urotensin-II does not respond to acute hemodynamic improvement. These findings suggest that urotensin-II does not play a major role in human CHF.     

Cardiovascular effects of training for a marathon run in unfit middle aged men.

The effects of a 30 week exercise programme on serum lipid values, blood pressure, and cardiac function were assessed in a group of sedentary men aged 35-50 training for their first marathon. Mean serum cholesterol concentration (n = 33) fell by 12% from 6.54 (SE 0.18) to 5.76 (0.15) mmol/l (mean fall 0.78 mmol/l; 95% confidence interval 0.52 to 1.04 mmol/l), serum triglyceride concentration (n = 33) by 22% from 1.56 (0.17) to 1.21 (0.09) mmol/l (mean fall 0.34 mmol/l; 95% confidence interval 0.12 to 0.56 mmol/l), and mean blood pressure (n = 27) by 10% from 102 (2) to 92 (2) mm Hg (mean fall 10 mm Hg; 95% confidence interval 7 to 13 mm Hg). These changes were not explained by changes in body composition. Peak exercise left ventricular end diastolic volume (n = 16) increased with training; as a result of this and an increased exercise left ventricular ejection fraction peak exercise cardiac output increased from 19.9 (1.2) to 23.1 (3.0) l/min (mean rise 3.2 l/min; 95% confidence interval 1.5 to 5.0 l/min). Maximum oxygen consumption increased from 33.9 (1.6) to 39.0 (1.3) ml/kg/min (mean rise 5.0 ml/kg/min; 95% confidence interval 1.8 to 8.2 ml/kg/min). This study showed favourable effects on coronary risk factors and cardiac function and supports the place of regular exercise in coronary prevention programmes.     

Mechanisms of oxygen demand/supply balance in the right ventricle

Few studies have investigated factors responsible for the O2 demand/supply balance in the right ventricle. Resting right coronary blood flow is lower than left coronary blood flow, which is consistent with the lesser work of the right ventricle. Because right and left coronary artery perfusion pressures are identical, right coronary conductance is less than left coronary conductance, but the signal relating this conductance to the lower right ventricular O2 demand has not been defined. At rest, the left ventricle extracts approximately 75% of the O2 delivered by coronary blood flow, whereas right ventricular O2 extraction is only ~50%. As a result, resting right coronary venous PO2 is approximately 30 mm Hg, whereas left coronary venous PO2 is approximately 20 mm Hg. Right coronary conductance does not sufficiently restrict flow to force the right ventricle to extract the same percentage of O2 as the left ventricle. Endogenous nitric oxide impacts the right ventricular O2 demand/supply balance by increasing the right coronary blood flow at rest and during acute pulmonary hypertension, systemic hypoxia, norepinephrine infusion, and coronary hypoperfusion. The substantial right ventricular O2 extraction reserve is used preferentially during exercise-induced increases in right ventricular myocardial O2 consumption. An augmented, sympathetic-mediated vasoconstrictor tone blunts metabolically mediated dilator mechanisms during exercise and forces the right ventricle to mobilize its O2 extraction reserve, but this tone does not limit resting right coronary flow. During exercise, right coronary vasodilation does not occur until right coronary venous PO2 decreases to approximately 20 mm Hg. The mechanism responsible for right coronary vasodilation at low PO2 has not been delineated. In the poorly autoregulating right coronary circulation, reduced coronary pressure unloads the coronary hydraulic skeleton and reduces right ventricular systolic stiffness. Thus, normal right ventricular external work and O2 demand/supply balance can be maintained during moderate coronary hypoperfusion.     

Effects of forskolin on placental vascular resistance in rabbits

Forskolin is a direct stimulant of adenylate cyclase and increases cAMP production. It also acts as a vasodilator. To study the effect of forskolin infusion on rabbit maternal vascular resistance, we instrumented 11 pregnant rabbits with catheters in the left ventricle, jugular vein, and left and right femoral arteries. After a 2-day recovery period, one of two protocols was performed. In the control period of the first protocol (N = 6), 50% ethanol in saline was infused at 0.103 ml.min-1 for 5-min. Forskolin (10(-3) M) in 50% ethanol was then infused for 5 min at 0.103 ml.min-1. After each infusion period, regional blood flows were measured by microsphere injection. Data are expressed as means +/- SEM. Blood pressure decreased from 81 +/- 3 to 79 +/- 3 mm Hg, (P less than 0.05, N = 10) during forskolin infusion. Total placental resistance fell from 180.3 +/- 10.7 to 133.8 +/- 12.0 mm Hg.min.ml-1 per gram, P less than 0.05. Cerebral, coronary, and renal vascular resistance fell significantly. During the second protocol (N = 5), angiotensin II (0.05 microgram.min-1) was infused for 5 min followed by the addition of forskolin (10(-3) M at 0.103 ml.min-1) to the infusate. Regional blood flows, vascular resistances and blood pressures were determined. Blood pressure fell from 99 +/- 6 to 92 +/- 7 mm Hg (P less than 0.05) when forskolin was added to the infusate. Placental resistance fell from 202.5 +/- 21.6 to 158.0 +/- 29.0 mm Hg.min.ml-1 per gram (P less than 0.05). While cerebral vascular resistance did not change, renal and coronary resistances fell in response to forskolin. This study demonstrates that forskolin is able to dilate rabbit placental vessels alone and in the presence of the vasoconstrictive agent angiotensin II.     

The cardiovascular response to lower body negative pressure in humans depends on seal location

We tested whether seal location at iliac crest (IC) or upper abdomen (UA), before and during lower body negative pressure (LBNP), would affect thoracic electrical impedance, hepatic blood flow, and central cardiovascular responses to LBNP. After 30 min of supine rest, LBNP at -40 mm Hg was applied for 15 min, either at IC or UA, in 14 healthy males. Plasma density and indocyanine green concentrations assessed plasma volume changes and hepatic perfusion. With both sealing types, LBNP-induced effects remained unchanged for mean arterial pressure (-3.0+/-1.1 mm Hg), cardiac output (-1.0 l min(-1)), and plasma volume (-11 %). Heart rate was greater during UA (80.6+/-3.3 bpm) than IC (76.0+/-2.5 bpm) (p<0.01) and thoracic impedance increased more using UA (3.2+/-0.2 Omega) than IC (1.8+/-0.2 Omega) (p<0.0001). Furthermore, during supine rest, UA was accompanied by lower thoracic impedance (26.9+/-1.1 vs 29.0+/-0.8 Omega, p<0.001) and hepatic perfusion (1.6 vs 1.8 l.min(-1), p<0.05) compared to IC. The data suggest that the reduction in central blood volume in response to LBNP depends on location of the applied seal. The sealing in itself altered blood volume distribution and hepatic perfusion in supine resting humans. Finally, application of LBNP with the seal at the upper abdomen induced a markedly larger reduction in central blood volume and greater increases in heart rate than when the seal was located at the iliac crest.     

Effect of posture on arterial baroreflex control of heart rate in humans

Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulate carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at +/- 15 degrees, +/- 30 degrees and +/- 45 degrees. During HDT at 15 degrees the pulse interval over the first 5 cardiac cycles following suction onset was 51 +/- (SEM) 18 ms longer (p less than 0.05), at 30 degrees it was 61 +/- 20 ms longer (p less than 0.05), and at 45 degrees it was 74 +/- 35 ms longer (p less than 0.01), compared with supine. During HUT at 15 degrees the pulse interval was 25 +/- 9 ms shorter (p less than 0.05) than when supine, but was not significantly different at 30 degrees and 45 degrees. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56 +/- 17 ms; less than 0.05), and after 40 min (25 +/- 9 ms; p less than 0.05) of 60 degrees HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model.

The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 +/- 0.34 micrograms/mL), mexiletine (n = 8, serum level 7.08 +/- 0.90 micrograms/mL), and quinidine (n = 6, serum level 6.8 +/- 1.22 micrograms/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4-10 Hz, 6-12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300-190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300-190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p less than 0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional asymmetry in carotid sinus cardiac reflexes in humans

The reflex cardiac response to activation (CBA) and inactivation (CBI) of the left and right carotid baroreceptors was studied in 30 healthy subjects, aged between 24 and 38 years. The CBA was evoked by applying negative pressure (from -20 to -60 mmHg) for 10 s to the left and right carotid sinus regions separately or both together, using two small neck capsules. The CBI was produced by applying left and right positive neck pressure (from 20 to 60 mmHg) for 10 s. The blood flow velocity was measured non-invasively with a Doppler scanner placed in the suprasternal notch. Blood flow acceleration was calculated and used as an indication of left cardiac contractility. Heart rate was measured continuously. Differences were found between right and left carotid sinus responses to CBA and CBI. The maximal response of the R-R interval was significantly greater during right CBA than during left CBA (the average gain: R-R.mmHg-1 2.69 ms.mmHg-1 and 1.75 ms.mmHg-1, respectively). Also, the reflex CBI response was significantly greater for the right (3.16 ms.mmHg-1) than for the left (2.22 ms.mmHg-1). The reflex decrease/increase in blood-flow acceleration in response to CBA/CBI was significantly greater during left than during right-sided activation/inactivation. It is suggested that the functional asymmetry was related to differences in right/left-sided cardiac innervation as well as to central ipsilateral projection of the carotid baroreceptor afferents to the nuclei tractus solitarii.     

Age-dependent relationship between the carotid intima-media thickness, baroreflex sensitivity, and the inter-beat interval in normotensive and hypertensive subjects

The interrelationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf), carotid wall thickness (IMT), and age was investigated in hypertensive and normotensive subjects with respect to the mean inter-beat interval (IBI) and blood pressure (BP). BP monitoring was performed in 25 treated hypertensives (Hy; 47.4+/-9.2 years of age) and 23 normotensives (Norm; 44.5+/-8.1 years). IMT was measured by ultrasonography. BRS and BRSf were determined by the spectral method (five-minute non-invasive beat-to-beat recording of BP and IBI, Finapres, controlled breathing at a frequency of 0.33 Hz). Significant differences between Hy and Norm were detected in IMT (Hy: 0.624+/-0.183, Norm: 0.522+/-0.070 mm; p<0.01), BRS (Hy: 3.5+/-1.6, Norm: 5.7+/-2.3 ms/mm Hg; p<0.01), BRSf (Hy: 0.005+/-0.002, Norm: 0.009+/-0.004 Hz/mm Hg; p<0.01), systolic BP (Hy: 131+/-21, Norm: 116+/-17 mm Hg; p<0.01) and diastolic BP (Hy: 77+/-16, Norm: 64+/-12 mm Hg; p<0.01). A significant correlation was found between age and IMT (Norm: 0.523, p<0.05; Hy+Norm: 0.419, p<0.01), age and BRS (Norm: -0.596, p< 0.01; Hy+Norm: -0.496, p<0.01), age and BRSf (Norm: -0.555, p<0.01; Hy: -0.540, p <0.01; Hy+Norm: -0.627, p<0.01), age and IBI (Hy: 0.478, p<0.05), age and diastolic BP (Hy: -0.454, p<0.05), BRS and IMT (Hy+Norm: -0.327, p<0.05) and BRSf and IMT (Hy+Norm: -0.358, p<0.05). Hypertensive patients have increased IMT and decreased BRS and BRSf. The positive correlation between age and IMT and the negative correlation between age and BRS and BRSf are in agreement with the hypothesis that the age-dependent decrease of baroreflex sensitivity corresponds to the age-related structural changes of the carotid wall. Using two indices of baroreflex sensitivity, BRS and BRSf, we could show that baroreflex sensitivity in hypertensives is lower not only due to thickening of the carotid wall, but also due to aging.     

Evaluation of digitalis in cardiac failure.

Ten patients in sinus rhythm with symptomatic cardiac failure participated in a study investigating the value of digitalis at rest and during dynamic exercise. A haemodynamic profile and left ventricular ejection fraction were measured before treatment, after intravenous ouabain, and after six weeks of maintenance treatment with digoxin. There was no significant change in the haemodynamic profile or in the left ventricular ejection fraction at rest after either glycoside. During exercise there was a significant reduction in left ventricular filling pressure from 39 +/- 3 mm Hg to 34 +/- 3 mm Hg (p less than 0.05) after ouabain and to 33 +/- 3 mm Hg (p less than 0.02) after digoxin. Cardiac index improved from 33 +/- 0.3 1/min/m2 to 4.0 +/- 0.4 l/min/m2 (p less than 0.01) after ouabain and to 3.8 +/- 0.4 l/min/m2 (p less than 0.01) after digoxin. During exercise stroke volume index and stroke work index also improved significantly with both glycosides. This was accompanied by an increase in left ventricular ejection fraction from 29 +/- 2% to 36 +/- 3% (p less than 0.05) after ouabain and digoxin. In this study both intravenous ouabain and maintenance treatment with oral digoxin exerted a modest positive inotropic effect in patients with cardiac failure in sinus rhythm. The haemodynamic benefit, however, was manifest only during exertion.     

Early changes of protein synthesis in myocardium and coronary arteries induced by NO synthase inhibition.

The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. N(G)-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8+/-2.0 to 149.4+/-3.9 mm Hg (p<0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8+/-1.1 to 175.0+/-5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4+/-5.3 to 147.6+/-4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9+/-0.7, 29.7+/-1.3 and 17.6+/-1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5+/-5.0, 33.5+/-2.6, 29.3+/-4.1%, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2+/-1.6% (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.     

Phase I and phase II of short-term mechanical restitution in perfused rat left ventricles

We examined the contributions of the Ca(2+) channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F(1)) were interpolated 40-600 ms following a steady-state beat (F(0)) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F(1)/F(0) versus the extrasystolic interval consisted of phase I, which occurred before relaxation of the steady-state beat, and phase II, which occurred later. Phase I exhibited a period of enhanced left ventricular pressure development that coincided with action potential prolongation. Phase I was eliminated by -BAY K 8644 (100 nM) and FPL 64176 (150 nM), augmented by 3 microM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca(2+) channel agonists and by isoproterenol but was eliminated by thapsigargin plus ryanodine. The results suggest that phase I of electromechanical restitution is caused by a transient L-type Ca(2+) current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca(2+).     

Intracoronary endothelin-1 infusion combined with systemic isoproterenol treatment: antagonistic arrhythmogenic effects

Endothelin-1 secretion and sympathetic activation may play important role in cardiovascular pathophysiology. In vivo interactions between these systems are not defined. We aimed to study the electrophysiological and haemodynamic effects of simultaneous intracoronary endothelin-1 and intravenous isoproterenol infusions. 18 anaesthetised open chest dogs were studied after AV-ablation. Mean arterial blood pressure, coronary blood flow, left ventricular contractility, standard electrocardiograms, right and left ventricular epi- and endocardial monophasic action potential (MAP) signals were recorded. Intracoronary endothelin-1 (30 pmol/min) was given to Group ET (n=6), intravenous isoproterenol (0.2 microg/kg/min) to Group ISO (n=6), both endothelin-1 and isoproterenol to Group ET+ISO (n=6) for 30 min. MAP duration increased in all studied regions of Group ET, decreased in all studied regions of Group ISO and ET+ISO (control vs. maximal changes of left ventricular epicardial MAP 90% duration, Group ET: 296+/-22 vs 369+/-20 ms, p<0.05, Group ISO: 298+/-18 vs 230+/-27 ms, p<0.01, Group ET+ISO: 302+/-18 vs 231+/-10 ms, p<0.01). In Group ET, early after depolarisations (3/6), polymorphic non-sustained ventricular tachycardias (6/6), and ventricular fibrillation (3/6) could be observed. In Group ISO, monomorphic non-sustained ventricular tachycardias (5/6) and atrial fibrillation (3/6) appeared. In Group ET+ISO, mono- and polymorphic non-sustained ventricular tachycardias occurred (5/6), neither ventricular fibrillation nor atrial fibrillation developed. An additive effect of endothelin-1 and isoproterenol on left ventricular contractility was observed. Isoproterenol treatment showed antagonistic effect against endothelin-1 induced MAP duration prolongation, early after depolarisation and ventricular fibrillation formation, while endothelin-1 showed protective effect against the development of isoproterenol induced atrial fibrillation.     

Non-invasive Determination of the Optimized Atrioventricular Delay in Patients with Implanted Biventricular Pacing Devices

Background

Biventricular (BiV) is extensively used in the treatment of congestive heart failure but so far no recommendations for optimized programming of atrioventricular-delay (AVD) settings have been proposed. Can AVD optimization be performed using a simple formula based on non-invasive doppler-echocardiography?

Methods

25 patients (ejection fraction 30±8%) received BiV ICDs. Doppler-echocardiographic evaluation of diastolic and systolic flow was performed for different AVDs (30ms to 150ms) and different stimulation sites (left ventricular (LV), right ventricular and BiV). The optimal atrioventricular delay was calculated applying a simple formula based on systolic and diastolic mechanical delays determined during doppler-echocardiography.

Results

The mean optimal AVD was calculated to be 112±29ms (50 to 180ms) for BiV, 95±30ms (65 to 150ms) for LV and 75±28ms (40 to 125ms) for right ventricular pacing with wide interindividual variations. Compared to suboptimal AVDs diastolic optimization improved preejection and ejection intervals independent to pacing site. Optimization of the AVD significantly increased ejection time during BiV pacing (279ms versus 266ms; p<0.05). Compared to LV or right ventricular pacing BiV pacing produced the shortest mean pre-ejection and longest ejection intervals as parameters of improved systolic ventricular contractile synchrony. Diastolic filling times were longest during BiV pacing compared to LV or RV pacing.

Conclusions

Individual programming of BiV pacing devices increases hemodynamic benefit when implementing the inter-individually widely varying electromechanical delays. Optimization applying a simple formula not only improves diastolic ventricular filling but also increases systolic functional parameters.     

右室间隔部起搏患者起搏QRS 波时限与心功能的关系

目的:探讨右室间隔部起搏患者起搏QRS波时限与心功能的关系。方法:回顾性分析植入右室间隔部起搏的双腔起搏器患者(111例),起搏器平均植入时间(4.52±3.65)年,通过常规体表心电图测得完全起搏时QRS波时限分为四组:A组为QRS≤120ms(21例);B组为120ms180ms(26例),行心脏彩色多普勒检查获取左房内径(LAD)、收缩末期左室内径(LVESD)、舒张末期左室内径(LVEDD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)及LVEF,同时检测患者的血清氨基末端脑肭肽前体(NT-proBNP),分析起搏QRS波时限与以上各指标的关系。结果:D组患者LAD、LVEDD、LVESD、IVST及IVPWT较其他三组明显增大,同时LVEF显著下降,NT-proBNP明显升高,有统计学意义(P<0.05)。同时发现随起搏QRS时限的不断增宽,不同组别的LVEF是依次降低(中位值分别为66.5%、60.3%、52.7%和45.8%),而血清NT-proBNP水平是依次增大(中位值分别为143.7 pg/ml、261.8 pg/ml、599.4 pg/m和971.2 pg/ml)。直线相关性分析示起搏QRS波时限与LAD(r=0.141,P<0.05)、LVEDd(r=0.678,P<0.05)、LVEDs(r=0.439,P<0.05)、IVST(r=0.165,P<0.05)及LVPWT(r=0.189,P<0.05)有显著线性关系,呈正相关。起搏QRS波时限与LVEF负相关(r=-0.684,P<0.05),起搏QRS波时限与NT-proBNP的对数正相关(r=0.368,P=0.029)。结论:对于右室间隔部起搏的双腔起搏患者,起搏QRS波时限是一个可初步判断心脏结构和功能的指标,其起搏QRS波时限延长可能会恶化患者的心脏结构及功能,可结合NT-proBNP进行动态观察,对起搏器植入患者的心功能恶化和心衰的预防有一定的临床实用价值。