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)     

SEQUENTIAL HEMODYNAMIC STUDIES OF THE IONESCU-SHILEY PERICARDIAL XENOGRAFT VALVE UP TO SIX YEARS AFTER IMPLANTATION

Sequential hemodynamic studies consisting of one preoperative and three postoperative cardiac catheterizations were undertaken in 19 patients at approximately 1, 4, and 6 years after valve replacement. Thirteen patients had aortic and six patients had mitral pericardial xenograft valves. Significant improvement was noted in various hemodynamic parameters in both groups of patients at the postoperative studies as compared to the preoperative findings. In patients with aortic valve replacement, the peak systolic gradient was 7.0 +/- 1.2 mm Hg at rest, and 10.0 +/- 1.6 mm Hg after exercise during the third postoperative study. The calculated xenograft orifice areas were 1.6 +/- 0.1 cm(2) at rest and 2.1 +/- 0.2 cm(2) after exercise in the aortic group, and 2.2 +/- 0.2 cm(2) at rest and 2.7 +/- 0.2 cm(2) after exercise in the mitral group at the third postoperative investigation. No significant change was noted among the three postoperative studies in the hemodynamic parameters. The results confirm the maintenance of functional performance of the Ionescu-Shiley pericardial xenograft up to 73 months after valve replacement.     

Oxygen and effective vasular compliance in acute heart failure.

The effect of hypoxemia on total vascular compliance was studied in anesthetized dogs using a venous bypass technique. Cardiac output was kept constant with an extracorporeal pump and respiration controlled to maintain normocapnia. When nitrogen was added to the respired gas to produce an arterial PO2 approximately 45 mm Hg, total vascular compliance was rapidly and significantly reduced to 0.93 ml (mm Hg)(-1) kg(-1) with incomplete recovery to baseline values of 1.30 plus or minus 0.06 ml (mm Hg)(-1) kg(-1) during subsequent ventilation with 100% oxygen. Acute heart failure was induced by gradual aortic constriction. Ventilation with 100% oxygen failed to prevent a gradual reduction in total vascular compliance to 0.86 ml (mm Hg)(-1) kg(-1) from a baseline value of 1.23 plus or minus 0.06 ml (mm Hg)(-1) kg(-1). Ventilation with 100% oxygen following the reduction in vascular compliance during acute heart failure also failed to significantly alter this parameter. Thus, improvement of arterial oxygen tension in patients with acute heart failure would be beneficial in providing greater oxygen delivery to the tissues without abolishing a compensatory mechanism of reduced vascular compliance which attempts to maintain a cardiac filling gradient of pressure.     

Intraaortic administration of protamine: Method for heparin neutralization after cardiopulmonary bypass

In neutralizing heparin with intravenous protamine sulfate, hypotension may be prevented by administering the drug intraarterially. Forty patients underwent cardiac surgery with extracorporeal circulation in our hospital; each received a rapid injection of nondiluted protamine sulfate in the aortic root to reverse the effects of heparin. To maintain the blood volume at a constant level, volume expanders and inotropic drugs were avoided. The intraaortic injections ranged in duration from 0.2 min to 2.8 min, with a mean of 1.1 min. The mean systolic pressure only dropped from 92 mm Hg (SD +/- 21) before protamine injection to 85 mm Hg (SD +/- 23) after injection (p < 0.0001). In seven patients (18%), no hypotension was evident; in the remaining patients, the systolic pressure returned to preinjection values within a mean of 2.2 min. Coagulation was observed within 3 to 4 min (mean = 2.2 min) after the initiation of injection. This study indicates that intraaortic administration of protamine is a rapid and safe technique for heparin reversal after cardiopulmonary bypass.     

Effects of parabolic flight on abdominal arterial pressure in conscious rats.

Abdominal arterial pressure during parabolic flight was measured using a telemetry system to clarify the acute effect of microgravity on hemodynamics in conscious rats. The microgravity condition was elicited by three different levels of entry gravity, i.e. 2 G, 1.5 G and 1 G. On exposure to 2 G, mean aortic pressure (MBP) increased up to 118.7 mm Hg +/- 7.3 compared with the value at 1 G (107.0 +/- 6.3 mm Hg, n=6). The value at microgravity preceded by 2 G was 118.0 mmHg +/- 5.2 mm HG and it was still higher than at 1 G. When 1.5 G was elicited before microgravity exposure, MBP also increased (1.5 G: 114.9 +/- 5.3 vs 1 G: 105.8+/-5.0 mm Hg) and the value at microgravity was 117.3 + /- 5.3 mmHg. During pre-microgravity maneuver with 1 G, no changes were observed compared with the control level at 1 G (pre-microgravity: 105.0 +/- 5.0 vs 1G: 104.8 +/- 5.1 mm Hg ), whereas the MBP increased up to 117.0 +/- 6.5 mm Hg on exposure to microgravity. From these results, we found that in conscious rat MBP increase during acute microgravity exposure with either 1 G or hyper-G entry.     

A new inorganic vasodilator, trans-[Ru(NO)(NH(3))(4)(POEt)(3)](PF(6))(3): hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models.

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.     

Intravenous diazoxide in treatment of hypertension associated with recent myocardial infarction

Twenty patients with blood pressure over 180/110 mm Hg one hour after admission to a coronary care unit with recent acute myocardial infarction were given intravenous diazoxide in a bolus of 300 mg. The average blood pressure before diazoxide was 194/122 mm Hg. Blood pressure fell considerably in all patients, though six patients required two injections. The average fall was 58 mm Hg systolic and 40 mm Hg diastolic. No patient became severely hypotensive. The heart rate increased by an average of 10 beats/min. In nine patients the electrocardiographic changes immediately after the administration of diazoxide suggested an increase in myocardial injury. Though none of the patients seemed to deteriorate clinically from the diazoxide the electrocardiographic changes suggested that the use of intravenous diazoxide to lower blood pressure in patients with acute myocardial infarction might possibly be deleterious.     

Cardiovascular responses to an isosterically modified prostaglandin analog in conscious dogs

The cardiovascular effects of oral and intravenous administration of 0.05 and 0.1 mg/kg of the isosterically modified prostaglandin (PG) analog, (+)- 4-(3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-thiazolidinyl] propyl) benzoic acid were ascertained in conscious mongrels. After 0.05 mg/kg p.o., mean arterial pressure (MAP), obtained from indwelling catheters, fell from 105 +/- 1 to 100 +/- 4 mm Hg and total peripheral resistance (TPR) decreased from 0.062 +/- 0.006 to 0.039 +/- 0.002 mm Hg/ml/min. Cardiac output (CO), measured via electromagnetic flow probes, rose from 1.8 +/- 0.2 to 2.6 +/- 0.1 l/min and heart rate from 109 +/- 13 to 128 +/- 8 beats/min. The 0.1 mg/kg p.o. dose produced similar results. Intravenous injection of 0.1 mg/kg immediately dropped MAP from 103 +/- 6 to 58 +/- 3 mm Hg and TPR from 0.049 +/- .006 to .014 +/- .002 mm Hg/ml/min. CO climbed from 2.3 +/- 0.2 to 5.3 +/- 0.5 l/min and HR increased from 126 +/- 9 to 254 +/- 14 beats/min. Stroke volume was not affected by either oral or intravenous administration of the PG analog. Pretreatment with 100 micrograms/kg timolol blunted the CO and HR responses to 0.1 mg/kg iv of the PG analog without affecting the depressor response. Metaraminol infused during injection of 0.1 mg/kg iv of the PG analog diminished all responses. When compared to the cardiovascular effects of hydralazine and nitroprusside, the profile of the PG analog activity closely resembled that produced by the arterial vasodilator, hydralazine; in contrast, nitroprusside (which also dilates veins) reduced stroke volume, but did not significantly affect HR. In conclusion, dilation of the resistance vessels by the PG analog decreased MAP and TPR and reflexly elevated CO and HR in conscious dogs.     

Impaired vascular dynamics in normotensive diabetic rats induced by streptozotocin: tapered T-tube model analysis

This study is to explore the changes of arterial mechanical properties in streptozotocin (STZ)-diabetic rats, based on the exponentially tapered T-tube model. Rats given STZ 65 mg kg(-1)i.v. are compared with untreated weight- and age-matched controls. A high-fidelity pressure sensor and electromagnetic flow probe measured pulsatile pressure and flow waves in the ascending aorta, respectively. Diabetic rats exhibit isobaric vasodilatation that is characterized by an increase in cardiac output and no significant changes in aortic pressure. Total peripheral resistance of diabetic rats is lower than that of weight- and age-matched controls. Diabetic rats have higher total peripheral compliance (2.86+/-0.70 microl mm Hg(-1)) than do weight- (1.77+/-0.34 microl mm Hg(-1)) and age-matched (1.87+/-0.69 microl mm Hg(-1)) controls. Aortic characteristic impedance is reduced from 0.017+/-0.003 mm Hg min kg ml(-1)in weight- and 0.020+/-0.004 mm Hg min kg ml(-1)in age-matched controls to 0.010+/-0.004 mm Hg min kg ml(-1)in diabetic rats. Moreover, diabetic rats show shorter wave transit time in lower body circulation (17.86+/-1.91 ms) than do weight- (20.45+/-1.91) and age-matched (23.05+/-2.04 ms) controls. Under isobaric vasodilatation, the decreased resistance and increased compliance in peripheral circulation suggest that the contractile dysfunction of the smooth muscle cells may occur in resistance arterioles in diabetes. With unaltered aortic pressure, an impairment in aortic distensibility of STZ-diabetic rats is manifest on the reduced wave transit time rather than on the diminished aortic characteristic impedance.     

Randomised controlled trial of computer assisted management of hypertension in primary care.

The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients'' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).     

Lack of additional action of oxygen on pulmonary artery pressure at the peak of verapamil or captopril action in pulmonary hypertension secondary to mitral stenosis]

The aim of the study was to investigate whether oxygen causes a further decrease in pulmonary artery pressure after administration of calcium channel blocker-verapamil-or angiotensin converting enzyme inhibitor-captopril-in the secondary pulmonary hypertension. We studied 37 patients with the secondary pulmonary hypertension (mean pulmonary artery systolic pressure = 56.1 mm Hg) due to mitral stenosis. After having completed hemodynamic diagnostic procedures, basal oxygen test was performed and pulmonary artery pressure was recorded at 10 min of oxygen breathing. Then, 10 mg of verapamil was injected into the pulmonary artery of 16 patients and 21 patients received 75 mg of oral captopril. At the peak of vasodilation, 30 min after verapamil and 90 min after captopril administration, pulmonary artery pressure was recorded and oxygen test was repeated. Baseline oxygen test produced a statistically significant decrease in pulmonary artery pressure. Verapamil and captopril also lowered pulmonary artery systolic and diastolic pressures. The second oxygen test did not cause a further decrease in the pulmonary artery pressure; mean pulmonary artery systolic pressure was 52.3 +/- 23.7 mm Hg, pulmonary artery diastolic pressure 22.7 +/- 10.6 mm Hg before and 49.1 +/- 23.8 mm Hg and 23.0 +/- 13.5 mm Hg, respectively after the test in verapamil group, and 47.0 +/- 15.5 mm Hg and 21.7 +/- 8.4 mm Hg before and 46.6 +/- 15.4 mm Hg, respectively in captopril subset. The results may support the thesis that vasodilating effect depends rather on the degree of pulmonary vascular changes than on the vasodilatory mechanism of particular drugs.     

The role of adrenergic innervation in distributing systemic and coronary fractions of left ventricular output under increased pressure in the ascending aorta

The significance of neurogenic influences upon the distribution of systemic and coronary fraction during rise of aortic pressure by step occlusion of ascending aorta was studied in anesthetized cats. Under elevation of aortic pressure up to 60 mm Hg the increase in systemic fraction and less pronounced rise of coronary fraction were observed. When aortic pressure elevation was more than 60 mm Hg commensurable increase of both fractions occurred. Under beta-adrenoreceptor blockade elevation of aortic pressure more than 60 mm Hg evoked the significant increase in systemic fraction and reduction in coronary fraction.     

Ionescu-Shiley pericardial xenograft valve: Hemodynamic evaluation and early clinical follow-up of 326 patients

Dissatisfaction with the hemodynamic characteristics of available porcine valves prompted a clinical trial of the Ionescu-Shiley percardial xenograft (ISPX) valve. Three hundred fifty-six ISPX valves were implanted consecutively in 326 patients. Operative mortality was 2.6% (2/75) for aortic valve replacement alone and 7.7% (12/155) for aortic valve replacements that included reoperations and combined procedures such as mitral commissurotomy, annuloplasty, and coronary artery bypass. Operative mortality for all patients who underwent mitral valve replacement was 9.5% (14/147). The mean peak systolic gradient pressure in the aortic position was 5.4 mm Hg overall and 4.27 mm Hg with the size 19 mm valve. There were no embolic episodes in patients who received the ISPX valve in the aortic position. The available data indicate that the rate of peripheral embolism with the ISPX valve compares favorably with that of porcine valves. Considering its hemodynamic advantage, if the longterm durability of the full-orifice Ionescu-Shiley pericardial xenograft valve continues to be confirmed by follow-up studies, it is our opinion that it is the biologic valve of choice.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Comparison of Central Aortic and Peripheral Artery Pressure Curves

Brachial artery and central aortic pressures were compared in 50 consecutive patients subjected to retrograde left heart catheterization in order to re-emphasize the fact that the two pressures are not necessarily identical. In 43 cases the systemic systolic pressure peaks exceeded those in the central aorta while in seven these pressures were equal. The average pressure difference was 22.6 mm. Hg. The greatest differences occurred in cases of aortic regurgitation and could be extreme, the brachial artery systolic pressure exceeding that in the aorta by more than 100 mm. Hg in some instances. The least differences occurred in cases of aortic stenosis but significant differences occasionally existed, leading to erroneous estimation of valve orifice size if the systemic rather than the aortic systolic pressure was used.     

Comparison of norepinephrine and serotonin vasoconstriction of the rat isolated testicular subcapsular artery at physiological and elevated transmural pressures.

This laboratory has previously described an in vitro preparation showing that the isolated testicular subcapsular artery of the adult rat has a novel triphasic transmural pressure-diameter myogenic response curve consisting of vasodilatation from 20 to 40 mm Hg, vasoconstriction from 40 to 100 mm Hg, and vasodilatation from 100 to 180 mm Hg, suggesting that the myogenic response of this artery between 40 and 100 mm Hg may have an important role in the autoregulation of the testicular blood supply. In the present studies, a 10-mm length of the adult rat isolated testicular subcapsular artery was cannulated and pressurized by an adjustable-height reservoir. External and internal arterial diameters were measured by a digital filar micrometer eyepiece. Dose-response curves for norepinephrine and serotonin were generated in a double-bath artery chamber at transmural pressures of 70 and 140 mm Hg, using half of the same artery for each pressure. Norepinephrine (3 x 10(-8) to 1 x 10(-5) M) produced a dose-dependent vasoconstriction at 70 mm Hg, with the highest dose causing a 31.4% decrease in lumen cross-sectional area (p < 0.05). Serotonin (3 x 10(-8) to 1 x 10(-6) M) produced a stronger dose-dependent vasoconstriction at 70 mm Hg, with the highest dose causing a 72.7% decrease in lumen cross-sectional area (p < 0.05). In marked contrast, the same concentration of norepinephrine and serotonin were found to have no statistically significant effect on the lumen cross-sectional area of the isolated testicular subcapsular artery at a transmural pressure of 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Telmisartan in the treatment of hypertension in patients with chronic renal insufficiency

The primary aim of this study was evaluation of the efficacy of telmisartan (angiotensin II receptor blocker- AT(1) blocker) on blood pressure in 10 patients with renal impairment in moderate or advanced stages of renal insufficiency and not dependent on haemodialysis. Its effect on proteinuria, renal function (represented by serum urea, creatinine, glomerular filtration), evaluation of overall therapy compliance in comparison with a previously prescribed angiotensin converting enzyme inhibitors (ACEI) were secondary aims. Considering the presence of left ventricle hypertrophy in all patients as a marker of hypertensive cardiopathy, the effect of telmisartan therapy on non-invasive cardiovascular parameters (ECG, echocardiography, and assessment of heart rate variability-HRV) was also evaluated. The study group involved 10 hypertensive patients (6 women, 4 men) with diabetic and non-diabetic renal impairment, proteinuria above 1 g/24 hours, hypertensive cardiopathy and intolerance of ACEI (cough). Telmisartan was added to their long-term antihypertensive combination therapy in a dose of 40 mg for the first 14 days, after which the dose increased to the maximal of 80 mg. The average initial daytime systolic blood pressure (SBP) was 149 +/- 19.7 mm Hg, average night-time SBP 145 +/- 23.0 mm Hg, average initial daytime diastolic BP (DBP) 90.6 +/- 2.5 mm Hg, night-time DBP 88.9 +/- 13.5 mm Hg. Average initial serum creatinine was 207.2 +/- 48.5 micromol/l, urea 15.1 +/- 4.4 mmol/l, GF 0.5 +/- 0.1 ml/s. Echocardiography revealed left ventricular (LV) hypertrophy with well preserved systolic and moderately impaired diastolic LV function. Also the HRV assessment revealed impaired neurovegetative (e.g. sympathovagal) balance. After 1 year of combination therapy with telmisartan, there was a clearly significant reduction in both SBP and DBP in both day and night-time (SBP daytime 149.6 vs.116.6 mm Hg, night-time 145.8 vs. 129.5 mm Hg; DBP daytime 90.6 vs. 83.5 mm Hg, night-time 88.9 vs. 79.3 mm Hg) and proteinuria (2.37 vs. 1.27 g/24 hour, p < 0.05). There were no significant changes in serum creatinine, urea values, and LV functions. On the other hand, further progression of the sympathovagal balance impairment was noted (continuing reduction of HRV in 9 from 10 patients), which can be described as the priority finding. The total compliance of telmisartan therapy was very good and without adverse clinical side effects. In conclusion - telmisartan reduces blood pressure and proteinuria safely and effectively in patients with various types of nephropathy in moderate or advanced stages of renal insufficiency.     

Cardiac dynamics of the Langendorff perfused heart

The Langendorff perfused heart is studied in a closed system with (i) automatic regulations to maintain constancy of the perfusion column (Krebs-Henseleit + 0.5% albumin or 25-30% washed erythrocyte suspension), (ii) continuous recording of rate, coronary flow, and supravalvular aortic pressure. A microcomputer with software interface is used for storage treatment and on-line analysis of the recorded variables. In 38 preparations perfused with Krebs-Henseleit, minimal diastolic (61.2 +/- 2.8 mm Hg) is significantly below and peak systolic (98.7 +/- 3.6 mm Hg) significantly above perfusion pressure (80 mm Hg). Pressure difference between minimal diastolic and peak systolic (delta P) is 37.5 +/- 1.8 mm Hg. Increases in perfusion pressure will be associated with increases of coronary flow and delta P, which is also increased by isoprenaline administration. Oxygen consumption decreased by 76% when perfusion pressure was lowered from 80 to 60 mm Hg in hearts perfused with a 30% erythrocyte suspension. All of these experimental results were interpreted as indicating that delta P measured in this system resulted from an ejected volume (x acceleration) from the heart. The ejected volume corresponds to a valvular leak caused by the rigid nature of the system which is devoid of aortic compliance. delta P may be considered an index of left ventricular performance, an indication that the Langendorff preparation studied under the present conditions is a working heart. A 100-microliter volume constant infusion syringe for time administration of cardioactive drugs may be inserted at the base of the perfusion column to obtain dose-response effects.     

The effects of changes in heart rate and aortic systolic pressure on left ventricular myocardial oxygen consumption in lambs

To determine whether changes in heart rate and aortic systolic pressure contribute equally to the determination of left ventricular myocardial oxygen consumption, we independently varied heart rate and pressure and compared the resultant oxygen consumption for similar rate-pressure products. In 6 young lambs which underwent atrioventricular node ablation, we varied heart rate by ventricular pacing at 250 beats/min, 300 beats/min, and 120 beats/min while aortic pressure remained stable and varied aortic systolic pressure by infusion of phenylephrine (to 132 +/- 15 mm Hg and 155 +/- 14 mm Hg) and by infusion of sodium nitroprusside (to 79 +/- 6 mm Hg) while heart rate was maintained stable at 200 beats/min. The 3 levels of change in aortic systolic pressure were chosen so that the ratepressure product during the pressure changes matched the rate-pressure product during the heart rate changes. We found that left ventricular myocardial oxygen consumption was the same at all 3 levels of the rate-pressure product whether heart rate was changed and pressure remained stable or pressure was changed and heart rate remained stable. Also, the correlation between oxygen consumption and the rate-pressure product was similar for both heart rate and pressure changes. During nitroprusside infusion at a fixed heart rate, oxygen extraction was significantly lower than during pacing at a heart rate of 120 beats/min when the rate-pressure product was comparable because of the direct vasodilatory effects of nitroprusside. We conclude that heart rate and aortic systolic pressure contribute equally to left ventricular myocardial oxygen consumption at the same rate-pressure product, even though there may be differences in myocardial blood flow and oxygen extraction.     

Systemic blood pressure response to the inhibition of two hyperpolarizing pathways: a comparison to NO-synthase inhibition

The impact on blood pressure of two vasodilating mechanisms, underlied by vascular smooth muscle hyperpolarization, was studied and compared to that induced by nitric oxide NO mechanism. Systemic blood pressure, after inhibitory intervention in arachidonic acid metabolism cytochrome P-450 inhibition by miconazole 0.5 mg/100 g b.w. , one of the hyperpolarizing pathways, did not change. After the inhibition of the action voltage-dependent K(+) channels operator by 4-aminopyridine 0.1 mg/100 g b.w. , the other hyperpolarizing pathway, blood pressure declined slightly from 132.3+/-3.2 mm Hg to 116.5+/-5.0 mm Hg, P<0.05 . Inhibition of nitric oxide production L-NAME 5 mg/100 g b.w. increased blood pressure considerably 123.5+/-2.7 mm Hg to 155.4+/-3.1 mm Hg, P<0.001 . After inhibition of the hyperpolarizing pathway by miconazole, hypotension induced by acetylcholine (Ach, 10 microg represented 63.0+/-1.9 mm Hg vs control value 78.6+/-5.2 mm Hg P<0.001 , by bradykinin (BK) 100 microg 59.4+/-3.9 mm Hg vs control value 71.2+/-6.1 mm Hg P<0.05 . After inhibition of the hyperpolarizing pathway by 4-aminopyridine, hypotension induced by ACh 10 microg achieved 64.6+/-2.5 mm Hg vs control value 78.4+/-2.8 mm Hg P<0.001 and that induced by BK 100 microg 56.6+/-5.3 mm Hg vs control value 72.3+/-2.5 mm Hg P<0.001 . ACh or BK hypotension after the inhibition of the above hyperpolarizing pathways was significantly attenuated. On the contrary, after NO-synthase inhibition the hypotension to ACh was significantly enhanced. Blood pressure decrease after ACh 10 microg hypotension was 91.8+/-4.1 mm Hg vs control value 79.3+/-3.3 mm Hg P<0.01 , and after BK 100 microg it was 78.4+/-7.1 mm Hg vs control value 68.3+/-5.2 mm Hg. A different basal BP response, but equally attenuated hypotension to Ach and BK, was detected after the inhibition of two selected hyperpolarizing pathways. In cotrast, the inhibition of NO production elicited an increase in systemic BP and augmentation of ACh and BK hypotension. The effectiveness of further hyperpolarizing mechanisms in relation to systemic BP regulation and nitric oxide level remains open.