Intramyocardial pressure and coronary extravascular resistance

Intramyocardial pressure is an indicator of coronary extravascular resistance. During systole, pressure in the subendocardium exceeds left ventricular intracavitary pressure; whereas pressure in the subepicardium is lower than left ventricular intracavitary pressure. Conversely, during diastole, subepicardial pressure exceeds both subendocardial pressure and left ventricular pressure. These observations suggest that coronary flow during systole is possible only in the subepicardial layers. During diastolic, however, a greater driving pressure is available for perfusion of the subendocardial layers relative to the subepicardial layers. On this basis, measurements of intramyocardial pressure contribute to an understanding of the mechanisms of regulation of the phasic and transmural distribution of coronary blow flow.     

Diastolic time fraction as a determinant of subendocardial perfusion

Diastolic time fraction (DTF) has been recognized as an important determinant for subendocardial perfusion, but microsphere studies in which DTF was the independent variable are practically absent. In 21 anesthetized goats, the left coronary main stem was artificially perfused at controlled pressure. DTF was varied by pacing the heart, vagus stimulation, or administration of dobutamine. Regional coronary flow was measured with fluorescent microspheres under full adenosine dilation. Perfusion pressure (P(c)) was defined as mean coronary arterial pressure minus minimal left ventricular pressure. Regional flow conductances (flow/P(c)) were as follows: for the subendocardium, C(endo) = -0.103 + 0.197 DTF + 0.00074 P(c) (P < 0.001); for the midmyocardium, conductance = -0.048 + 0.126 DTF + 0.00049 P(c) (P < 0.001); and for the subepicardium, C(epi) was not significant. C(endo)-DTF relations demonstrated a finite value for DTF at which flow is zero, implying that, at physiological pressures, systolic subendocardial flow limitation extends into diastole. The DTF corresponding to an equal conductance in subendocardium and subepicardium (DTF1) was inversely related to P(c): DTF1 = 0.78 - 0.003 P(c) (P < 0.01). When heart rate and P(c) were held constant and dobutamine was administered (5 goats), contractility doubled and DTF increased by 39%, resulting in an increase of C(endo) of 40%. It is concluded that 1) DTF is a determinant of subendocardial perfusion, 2) systolic compression exerts a flow-limiting effect into diastole, and 3) corresponding to clinical findings on inducible ischemia we predict that, under hyperemic conditions, C(endo) < C(epi) if P(c) is lower than approximately 75% of a normal aortic pressure and heart rate >80 beats/min.     

Myocardial tissue pressure and blood flow during coronary sinus pressure modulation in anesthetized dogs.

To determine whether coronary sinus outflow pressure (Pcs) or intramyocardial tissue pressure (IMP) is the effective back pressure in the different layers of the left ventricular (LV) myocardium, we increased Pcs in 14 open-chest dogs under maximal coronary artery vasodilation. Circumflex arterial (flowmeter), LV total, and subendocardial and subepicardial (15-microns radioactive spheres) pressure-flow relationships (PFR) and IMP (needle-tip pressure transducers) were recorded during graded constriction of the artery at two diastolic Pcs levels (7 +/- 3 vs. 23 +/- 4 mmHg). At high Pcs, LV, aortic and diastolic circumflex arterial pressure, heart rate, myocardial oxygen consumption, and lactate extraction were unchanged; IMP in the subendocardium did not change (130/19 mmHg), whereas IMP in the subepicardium increased by 17 mmHg during systole and 10 mmHg during diastole (P < or = 0.001), independently of circumflex arterial pressure. Increasing Pcs did not change the slope of the PFR; however, coronary pressure at zero flow increased in the subepicardium (P < or = 0.008), whereas in the subendocardium it remained unchanged at 24 +/- 3 mmHg. Thus Pcs can regulate IMP independently of circumflex arterial pressure and consequently influence myocardial perfusion, especially in the subepicardial tissue layer of the LV.     

Dynamics of flow velocities in endocardial and epicardial coronary arterioles

The subendocardium is the most vulnerable area of the left ventricle to the effects of hypoperfusion and ischemia. Despite this well-acknowledged observation, the mechanisms underlying this susceptibility are not elucidated, although numerous explanations including differences in transmural distribution of hemodynamics, metabolism, and wall stresses have been proposed. Our goal was to make dynamic measurements of endocardial and epicardial flow velocities, which reflect hemodynamic and wall stresses, to approach this problem. We measured blood flow velocities in subendocardial and subepicardial coronary arterioles of in vivo beating canine hearts using a high-speed, charge-coupled device, intravital videomicroscope with a rod-probe lens. Subendocardial flow was characterized by remarkable systolic flow-velocity reversal (systolic slosh ratio, 84%; measurable velocity of retrograde flow, faster than -40 mm/s), which contrasted to predominant forward-flow velocity during systole in the subepicardial arterioles (systolic slosh ratio, 25%; maximum velocity, approximately -20 mm/s; P < 0.0005 and 0.05 vs. subendocardial arterioles, respectively). We speculate that this retrograde flow is "wasteful," because this volume must be refilled during the subsequent diastole, which thereby detracts from the net perfusion as well as the time for perfusion. Accordingly, we also believe that the retrograde systolic blood flow contributes to the vulnerability of the subendocardium to ischemia.     

Stenosis differentially affects subendocardial and subepicardial arterioles in vivo

The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.     

Effects of coronary sinus pressure elevation on coronary blood flow distribution in dogs with normal preload

Coronary sinus pressure (Pcs) elevation shifts the diastolic coronary pressure-flow relation (PFR) of the entire left ventricular myocardium to a higher pressure intercept. This finding suggests that Pcs is one determinant of zero-flow pressure (Pzf) and challenges the existence of a vascular waterfall mechanism in the coronary circulation. To determine whether coronary sinus or tissue pressure is the effective coronary back pressure in different layers of the left ventricular myocardium, the effect of increasing Pcs was studied while left ventricular preload was low. PFRs were determined experimentally by graded constriction of the circumflex coronary artery while measuring flow using a flowmeter. Transmural myocardial blood flow distribution was studied (15-micron radioactive spheres) at steady state, during maximal coronary artery vasodilatation at three points on the linear portion of the circumflex PFR both at low and high diastolic Pcs (7 +/- 3 vs. 22 +/- 5 mmHg; p less than 0.0001) (1 mmHg = 133.322 Pa). In the uninstrumented anterior wall the blood flow measurements were obtained in triplicate at the two Pcs levels. From low to high Pcs, mean aortic (98 +/- 23 mmHg) and left atrial (5 +/- 3 mmHg) pressure, percent diastolic time (49 +/- 7%), percent left ventricular wall thickening (32 +/- 4%), and percent myocardial lactate extraction (15 +/- 12%) were not significantly changed. Increasing Pcs did not alter the slope of the PFR; however, the Pzf increased in the subepicardial layer (p less than 0.0001), whereas in the subendocardial layer Pzf did not change significantly. Similar slopes and Pzf were observed for the PFR of both total myocardial mass and subepicardial region at low and high Pcs. Subendocardial:subepicardial blood flow ratios increased for each set of measurements when Pcs was elevated (p less than 0.0001), owing to a reduction of subepicardial blood flow; however, subendocardial blood flow remained unchanged, while starting in the subepicardium toward midmyocardium blood flow decreased at high Pcs. This pattern was similar for the uninstrumented anterior wall as well as in the posterior wall. Thus as Pcs increases it becomes the effective coronary back pressure with decreasing magnitude from the subepicardium toward the subendocardium of the left ventricle. Assuming that elevating Pcs results in transmural elevation in coronary venous pressure, these findings support the hypothesis of a differential intramyocardial waterfall mechanism with greater subendo- than subepi-cardial tissue pressure.     

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.     

Effect of magnesium sulfate administration on subendocardial and subepicardial perfusion

The objective of this study was to determine the effect of systemic MgSO₄ infusion on subendocardial and subepicardial perfusion. Seventeen spontaneously breathing piglets were examined. Myocardial perfusion was measured using radiolabeled microspheres at baseline, 30 and 60 min after either MgSO₄ (80 mg/kg) or saline infusion. Blood pressure, heart rate, and cardiac output were also measured at these time intervals. Comparison of the magnesiuminduced changes in systemic blood pressure and on subendocardial and subepicardial perfusion at 30 and 60 min with values obtained with saline solution at 30 and 60 min, yielded no statistically significant difference (Tables 1–3). The ratio of subendocardial/subepicardial blood flow and subendocardial and subepicardial coronary vascular resistance at 30 and 60 min revealed no statistically significant differences between the magnesium and the control group (Table 3). There were no statistically significant difference in cardiac output and heart rate during any of the measured periods (Table 2). Our results suggest that the administration of MgSO₄ does not alter the ratio of subendocardial/subepicardial blood flow and the ratio of subendocardial/subepicardial coronary vascular resistance.     

Transmural sheet strains in the lateral wall of the ovine left ventricle

In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.     

Why is the subendocardium more vulnerable to ischemia? A new paradigm

Myocardial ischemia is transmurally heterogeneous where the subendocardium is at higher risk. Stenosis induces reduced perfusion pressure, blood flow redistribution away from the subendocardium, and consequent subendocardial vulnerability. We propose that the flow redistribution stems from the higher compliance of the subendocardial vasculature. This new paradigm was tested using network flow simulation based on measured coronary anatomy, vessel flow and mechanics, and myocardium-vessel interactions. Flow redistribution was quantified by the relative change in the subendocardial-to-subepicardial perfusion ratio under a 60-mmHg perfusion pressure reduction. Myocardial contraction was found to induce the following: 1) more compressive loading and subsequent lower transvascular pressure in deeper vessels, 2) consequent higher compliance of the subendocardial vasculature, and 3) substantial flow redistribution, i.e., a 20% drop in the subendocardial-to-subepicardial flow ratio under the prescribed reduction in perfusion pressure. This flow redistribution was found to occur primarily because the vessel compliance is nonlinear (pressure dependent). The observed thinner subendocardial vessel walls were predicted to induce a higher compliance of the subendocardial vasculature and greater flow redistribution. Subendocardial perfusion was predicted to improve with a reduction of either heart rate or left ventricular pressure under low perfusion pressure. In conclusion, subendocardial vulnerability to a acute reduction in perfusion pressure stems primarily from differences in vascular compliance induced by transmural differences in both extravascular loading and vessel wall thickness. Subendocardial ischemia can be improved by a reduction of heart rate and left ventricular pressure.     

Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy

Hypertension-induced cardiac hypertrophy alters the amplitude and time course of the systolic Ca2+ transient of subepicardial and subendocardial ventricular myocytes. The present study was designed to elucidate the mechanisms underlying these changes. Myocytes were isolated from the left ventricular subepicardium and subendocardium of 20-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY; control). We monitored intracellular Ca2+ using fluo 3 or fura 2; caffeine (20 mmol/l) was used to release Ca2+ from the sarcoplasmic reticulum (SR), and Ni2+ (10 mM) was used to inhibit Na+/Ca2+ exchange (NCX) function. SHR myocytes were significantly larger than those from WKY hearts, consistent with cellular hypertrophy. Subepicardial myocytes from SHR hearts showed larger Ca2+ transient amplitude and SR Ca2+ content and less Ca2+ extrusion via NCX compared with subepicardial WKY myocytes. These parameters did not change in subendocardial myocytes. The time course of decline of the Ca2+ transient was the same in all groups of cells, but its time to peak was shorter in subepicardial cells than in subendocardial cells in WKY and SHR and was slightly prolonged in subendocardial SHR cells compared with WKY subendocardial myocytes. It is concluded that the major change in Ca2+ cycling during compensated hypertrophy in SHR is a decrease in NCX activity in subepicardial cells; this increases SR Ca2+ content and hence Ca2+ transient amplitude, thus helping to maintain the strength of contraction in the face of an increased afterload.     

Coronary circulatory pressure gradients

The pressure gradients of the canine coronary circulation were measured in 37 dogs during control and following eight interventions: left stellate ganglion or left vagosympathetic trunk stimulation, as well as isoproterenol, acetylcholine, noradrenaline, adenosine, phenylephrine, or adrenaline infusions. During control, pressure gradients in the epicardial coronary arteries (measured from the aorta to coronary artery branch) were 15.2 +/- 1 mmHg (1 mmHg (1 mmHg = 133.32 Pa) during systole and 10.6 +/- 1.5 mmHg during diastole. Adrenaline increased this systolic gradient, while acetylcholine and phenylephrine decreased it. In contrast, the pressure gradients in the small coronary arteries (from the branch of an epicardial artery to the pressure in an obstructed coronary artery) were 56 +/- 1.3 mmHg during systole and 63.7 +/- 1.3 mmHg during diastole. These gradients were increased by phenylephrine during both systole and diastole, noradrenaline and adrenaline during diastole and decreased by isoproterenol (systolic), left vagosympathetic trunk stimulation (diastolic), acetylcholine (systolic and diastolic), and adenosine (diastolic). The microcirculation and small vein gradients during control were 16.4 +/- 1.2 mmHg during systole and 8.5 +/- 0.8 mmHg during diastole. Decreases in this gradient were produced by isoproterenol, acetylcholine, and adenosine during systole and adenosine during diastole. These observations are consistent with the concept that the coronary circulation has considerable regulatory capacity in all of its component parts. Specifically, epicardial arteries appear to function as both conduits and as resistance vessels, small arteries as major resistance vessels, and the microcirculation and small veins as both capacitors and resistors.     

Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.     

ECG-synchronized thoracic vest inflation during autonomic blockade, myocardial ischemia, or cardiac arrest.

To evaluate, in the absence of lung inflation, the cardiovascular effects of single and repetitive pleural pressure increments induced by thoracic vest inflations and timed to occur during specific portions of the cardiac cycle, seven chronically instrumented dogs were studied. Reflexes and left ventricular (LV) performance were varied by autonomic blockade, circumflex coronary occlusion (with and without beta-blockade), or cardiac arrest. Single late systolic, but not early systolic, vest inflations significantly increased LV stroke volume both before (+12.4%) and after myocardial depression by coronary occlusion+beta-blockade (+18.5%) when performed after a period of apnea to control preload and rate. During vest inflations, LV and aortic pressures increased to a greater degree than esophageal pressure (by 51 vs. 39 mmHg, P = 0.0001). Lung inflations (26 trials in 3 dogs) during early or late systole failed to increase stroke volume, despite peak esophageal pressures of 11-26 mmHg. With autonomic reflexes intact, repetitive vest inflations coupled to early systole, late systole, or diastole induced a large (40%) but unspecific systemic flow increase. In contrast, during autonomic blockade, flow increased slightly (7.5%, P < 0.05) with late systolic compared with diastolic inflations but not relative to baseline. During coronary occlusion (with or without beta-blockade), no cycle-specific differences were seen, whereas matched vest inflations during cardiac arrest generated 20-30% of normal systemic flow. Thus only single late systolic thoracic vest inflations associated with large increments in pleural pressure increased LV emptying, presumably by decreasing LV afterload and/or focal cardiac compression. However, during myocardial ischemia and depression, coupling of vest inflation to specific parts of the cardiac cycle revealed no hemodynamic improvement, suggesting that benefits of this circulatory assist method, if any, are minor and may be restricted to conditions of cardiac arrest.     

Contribution of laminar myofiber architecture to load-dependent changes in mechanics of LV myocardium

The ventricular myocardium consists of a syncytium of myocytes organized into branching, transmurally oriented laminar sheets approximately four cells thick. When systolic deformation is expressed in an axis system determined by the anatomy of the laminar architecture, laminar sheets of myocytes shear and laterally extend in an approximately radial direction. These deformations account for ~90% of normal systolic wall thickening in the left ventricular free wall. In the present study, we investigated whether the changes in systolic and diastolic function of the sheets were sensitive to alterations in systolic and diastolic load. Our results indicate that there is substantial reorientation of the laminar architecture during systole and diastole. Moreover, this reorientation is both site and load dependent. Thus as end-diastolic pressure is increased and the left ventricular wall thins, sheets shorten and rotate away from the radial direction due to transverse shearing, opposite of what occurs in systole. Both mechanisms of thickening contribute substantially to normal left ventricular wall function. Whereas the relative contributions of shear and extension are comparable at the base, sheet shear is the predominant factor at the apex. The magnitude of shortening/extension and shear increases with preload and decreases with afterload. These findings underscore the essential contribution of the laminar myocardial architecture for normal ventricular function throughout the cardiac cycle.     

Coronary artery compliance in the dog

Measurement of left anterior descending coronary arterial pressure, phasic coronary flow, and intramyocardial pressure in an open-chest dog provided data, which when entered into the computer model of the coronary circulation, permitted calculation of coronary artery compliance and resistance during systole and diastole. Resting in vivo compliance averaged 0.21 x 10(-3) mL/mmHg (1 mmHg = 133.322 Pa) while systolic resistance averaged 4.05 mmHg X min-1 X mL-1 and during diastole 2.06 mmHg X min-1 X mL-1. Left stellate ganglion stimulation or vasodilation caused minimal changes in compliance but glutaraldehyde applied to arterial wall caused a decrease in compliance. Sympathetic stimulation and vasodilation decreased both diastolic and systolic resistance. Transmural distribution of coronary flow was not significantly altered by the experimental changes in compliance and resistance.     

Regulation of transmural myocardial blood flow

A major problem in understanding how myocardial blood flow is regulated is the common occurrence of subendocardial ischemia in many diseases, with or without coronary arterial disease. Two commonly held explanatory hypotheses were that high systolic intramyocardial pressures prevented flow to deep but not superficial muscle, or that in diastole tissue pressures were highest subendocardially. Neither hypothesis is tenable today, and the likeliest hypothesis is that retrograde systolic flow from the deeper muscle produces a longer time constant for diastolic flow in deep than in superficial muscle.     

Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar (P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole (P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.     

Transient analysis of cardiopulmonary interactions. II. Systolic events

The etiology of the fall in left ventricular stroke volume (LVSV) and arterial pressure with a negative intrathoracic pressure (NITP) during inspiration is controversial. An increase in LV afterload produced by NITP has been proposed as one explanation but is difficult to evaluate if preload is also altered. To test the hypothesis that a systolic event alone, i.e., a change in LV afterload or contractility, can reduce LVSV during inspiration independent of changes in LV preload, a rapid transient NITP confined to systole was produced by electrocardiogram-triggered phrenic nerve stimulation in eight anesthetized dogs. Intrathoracic descending aortic diameters were measured by sonomicrometry to transduce qualitative changes in aortic transmural pressure. With the airway completely obstructed systolic NITP resulted in a decrease in LVSV (-8.1%, P less than 0.001) but an increase in the systolic anteroposterior (0.54 mm, P less than 0.01) and right-to-left (0.45 mm, P less than 0.01) aortic diameters compared with preceding beat. Similar significant changes were observed with the airway unobstructed. These observations are consistent with an increased afterload imposed on the LV reducing LVSV and egress of blood out of the thorax. Prolonging NITP to include both systole and diastole, a profound fall in LVSV is observed, consistent with the independent influences of systolic and diastolic events combining to diminish LVSV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of timing and velocity of impact on ventricular myocardial rupture

The effects of impact timing during the cardiac cycle on the sensitivity of the heart to impact-induced rupture was investigated in an open-chest animal model. Direct mechanical impacts were applied to two adjacent sites on the exposed left ventricular surface at the end of systole or diastole. Impacts at 5 m/s and a contact stroke of 5 cm at the end of systole resulted in no cardiac rupture in seven animals, whereas similar impacts at the end of diastole resulted in six cardiac ruptures. Direct impact at 15 m/s and a contact stroke of 2 cm at the end of either systole or diastole resulted in perforationlike cardiac rupture in all attempts. At low-impact velocity the heart was observed in high-speed movie to bounce away from the impact interface during a systolic impact, but deform around the impactor during a diastolic impact. The heart generally remained motionless during the downward impact stroke at high-impact velocity in either a systolic or diastolic impact. The lower ventricular pressure, reduced muscle stiffness, thinner myocardial wall and larger mass of the filled ventricle probably contributed to a greater sensitivity of the heart to rupture in diastole at low-impact velocity. However, the same factors had no role at high-impact velocity.