Systolic Segment Length Shortening Research Articles

Haemodynamic changes during halothane, sevoflurane and desflurane anaesthesia in dogs before and after the induction of severe heart failure

The effects of desflurane and sevoflurane on the failing myocardium are still uncertain. We investigated the effects of different concentrations of sevoflurane, desflurane and halothane in dogs with pacing induced chronic heart failure. Global (left ventricular pressure, left ventricular dP/dt, Konigsbergtransducer) and regional myocardial function (systolic segment length shortening, ultrasonic crystals) were measured in chronically instrumented dogs with tachycardia induced severe congestive heart failure. Measurements were performed in healthy dogs and after induction of heart failure in the awake state and during anaesthesia with 0.75, 1.0, 1.25 and 1.75 minimum alveolar concentration (MAC) of halothane, sevoflurane or desflurane. The anaesthetics reduced dP/dtmax in a dose-dependent manner in healthy dogs (dP/dtmax decreased to 43-53% of awake values at 1.75 MAC). Chronic rapid left ventricular pacing increased heart rate and left ventricular end-diastolic pressure and decreased mean arterial pressure, left ventricular systolic pressure and dP/dtmax. The reduction in contractility was similar in the failing myocardium (to 41-50% of awake values at 1.75 MAC). Segmental shortening was reduced during anaesthesia by 50-62% after pacing compared with 22-44% in normal hearts. While there were similar effects of the different anaesthetics on diastolic function in healthy dogs, after induction of heart failure a more pronounced increase of the time constant of isovolumic relaxation and a greater decrease of dP/dtmin was observed with sevoflurane than with desflurane, indicating a stronger depression of diastolic function. While the negative inotropic effects of sevoflurane and desflurane were similar in normal and in the failing myocardium in vivo, desflurane led to a better preservation of diastolic function in the failing myocardium.

Effect of arterial blood pressure and ventilation gases on cardiac depression induced by coronary air embolism

In this study the time course of cardiac depression after selective intracoronary injection of air bubbles was investigated in six anesthetized pigs (30 +/- 2 kg) with different mixtures of ventilation gases and different mean arterial blood pressures (MAP). Air bubbles of 150 microns diam were injected into the left anterior descending coronary artery (LADCA) in a volume of 2 microliters/kg body wt. In each animal an injection of air bubbles was applied during ventilation with N2-O2 and a MAP of 77 +/- 3 mmHg (N2-O2/low pressure) or 111 +/- 3 mmHg (N2-O2/high pressure) and during ventilation with pure O2 and a MAP of 77 +/- 3 mmHg (O2/low pressure) or 110 +/- 3 mmHg (O2/high pressure). Systemic hemodynamic variables such as left ventricular pressure, its peak first derivatives, and MAP changed < 10% after injection of air bubbles. During N2-O2/low pressure, systolic segment length shortening in the LADCA region (SS-LADCA) decreased from baseline and did not return to baseline within the 10 min after injection of air bubbles. During N2-O2/high pressure and O2/low pressure, SS-LADCA was decreased between 60 and 120 s, whereas for O2/high pressure this period was from 60 to 90 s. By calculating the time integral of the deviation from baseline of SS-LADCA, it could be demonstrated that the depression of regional myocardial function was less severe during O2/high pressure and O2/low pressure than during N2-O2/low pressure. We conclude that, when coronary air embolism occurs during hypertension and during ventilation with pure O2 instead of a normal N2-O2 mixture, the resulting depression of regional myocardial function is reduced.

Cardiac contractile function following repetitive brief ischemia: effects of nucleoside transport inhibition.

The effects of nucleoside transport inhibition on cardiac contractile function were examined in anesthetized pigs subjected to five 6-min left anterior descending coronary artery (LAD) occlusions, separated by 20-min reperfusion, and followed by 150-min reperfusion. In group 1 (n = 8), saline was infused. In group 2 (n = 9), endogenous myocardial accumulation of adenosine was increased by intracoronary infusion of the specific nucleoside transport inhibitor R-75 231. Left ventricular segment lengths were recorded by ultrasonic crystals in the inner one-third of the myocardium. Percent systolic segment length shortening (SS) (normalized to percent of preischemic value) was significantly better maintained in the R-75 231 group compared with the saline group after each occlusion. SS in the saline group reached a nadir of 30% (22-40) at 30-min reperfusion after the last occlusion compared with 66% (54-73) in the R-75 231 group. In the R-75 231 group, but not in the saline group, maximal postischemic decline in SS and decline at 20-min reperfusion were significantly reduced following the last occlusion. We conclude that R-75 231, which inhibits nucleoside transport, attenuates contractile dysfunction following repetitive brief ischemia and results in a preconditioning-like effect against stunning in the pig. On the basis of the well-documented biochemical effects of R-75 231, increased accumulation of endogenous adenosine most likely explains these findings.

Intracoronary trimetazidine does not improve recovery of regional function in a porcine model of repeated ischemia

We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 micrograms/kg/min, n = 6) or saline (1 ml/min, n = 7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals. In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/dtmax, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p < 0.05). Systolic segment length shortening and EW were increased at the end of the first occlusion-reperfusion cycle, decreased gradually during the remainder of the occlusion-reperfusion periods, and did not improve during the recovery period. Energy charge and myocardial blood flow were not impaired, but oxygen consumption was decreased during the recovery period. The malondialdehyde data did not provide evidence for production of oxygen free radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

L-propionylcarnitine and myocardial performance in stunned porcine myocardium.

Recently, we showed that L-propionylcarnitine did not affect recovery of regional contractile function of porcine myocardium subjected to 1 h of low-flow ischemia followed by 2 hr of reperfusion. In that study, ischemia may have been too severe and/or the duration of reperfusion too short to detect a beneficial effect of the compound. Therefore, in the present study we investigated the effects of saline (control group; n = 14) or pretreatment with L-propionyl-carnitine (3 days of 50 mg/kg p.o. b.i.d. + 50 mg/kg i.v. prior to the experiment; n = 13) on recovery of regional contractile function of the myocardium in open-chest anesthetized pigs, subjected to two cycles of 10 min of left anterior descending coronary artery (LADCA) occlusion, each followed by 30 min of reperfusion. In the control animals, at the end of the second reperfusion period, systemic vascular resistance had increased by 18%, which, however, was not observed in the L-propionylcarnitine-treated pigs. In the control group, during the first occlusion, systolic segment length shortening (SSLS) of the LADCA-perfused area decreased from 18.5 +/- 5.5% to -3.7 = 3.2%. After 30 min of reperfusion, SSLS of the LADCA-perfused area had only partially recovered to 6.2 +/- 5.9%. During the second occlusion-reperfusion cycle similar values for SSLS were observed. In the treated animals, SSLS of the LADCA-perfused area was slightly improved after the second occlusion-reperfusion cycle (p = 0.056). This effect did not result in an overall improvement in cardiac pump function.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of adenosine for reactive hyperemia in normal and stunned porcine myocardium.

The role of adenosine for reactive hyperemia in normal and stunned myocardium was examined in 16 open-chest barbiturate-anesthetized pigs. Interstitial adenosine concentration was reduced or enhanced by intracoronary infusion of adenosine deaminase or the nucleoside transport inhibitor R 75231, respectively. In normal myocardium, adenosine deaminase reduced volume of hyperemia (Doppler flowmetry) after a 30-s left anterior descending coronary artery (LAD) occlusion by 20% (6-34%; P < 0.05), whereas R 75231 increased volume of hyperemia by 15% (2-24%; P < 0.05). Adenosine deaminase reduced volume of hyperemia after a 2-min LAD occlusion by 27% (13-37%; P < 0.001), whereas R 75231 increased volume of hyperemia by 66% (53-159%; P < 0.001). Adenosine deaminase and R 75231 did not affect maximal hyperemia. Volume of hyperemia after a 2-min LAD occlusion was reduced in stunned myocardium (%systolic segment length shortening reduced by approximately 45%, ultrasonic technique) but not further altered by either adenosine deaminase or R 75231. These findings show that adenosine contributes to reactive hyperemia after 30-120 s of ischemia in normal myocardium and indicate that the reduced reactive hyperemia in stunned myocardium is due to reduced accumulation of adenosine during ischemia.

Characteristics and development of myocardial stunning in the pig.

Regional left ventricular function associated with consecutive ischemic periods of 2, 2, 5, 10, and 2 min was recorded by ultrasonic technique in pentobarbital-anesthetized pigs. All systolic and diastolic derangements first appeared after 5 min of ischemia, and all worsened after 10 min of ischemia. Percent systolic segment length shortening reached nadirs 23 (17-29)% (P less than 0.001) and 54 (45-65)% (P less than 0.001) below baseline 30 min after 5 and 10 min of ischemia. During reperfusion all recorded systolic and diastolic variables transiently recovered and then deteriorated with a closely similar time course. This covariance indicates that systolic and diastolic derangements are causally related, and because diastolic compliance was preserved in stunned myocardium we conclude that all derangements largely result from reduced systolic tension development. Transient postischemic hypercontractility followed all occlusions and was not attenuated by beta-blockade and not mimicked by hyperemia alone. Postischemic hypercontractility was greatly enhanced in stunned myocardium, and we hypothesize that more pronounced and sustained postischemic elevation of intracellular Ca2+ concentration explains this observation.

Canine coronary vasodepressor responses to hypoxia are attenuated but not abolished by 8-phenyltheophylline.

The purpose of this study was twofold: 1) to verify a report that a suspension of 8-phenyltheophylline (8-PT) completely abolished hypoxia-induced coronary vasodilation [H. M. Wei, Y. H. Kang, and G. F. Merrill. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1043-H1048, 1989] and 2) to determine the effect of dissolved 8-PT on hypoxic hyperemia. The left anterior descending coronary artery of anesthetized dogs was cannulated and perfused at either constant flow or constant pressure. An 8-PT suspension (40 micrograms.kg-1.min-1) produced a twofold elevation of coronary perfusion pressure at constant flow, a 97% decrease in coronary flow at constant pressure, and regional akinesia in both conditions. The coronary vasculature was unresponsive to 60-s coronary occlusion, exogenous adenosine, and hypoxia after infusion of the 8-PT suspension. These findings are consistent with obstruction of the coronary microvasculature by the 8-PT suspension. An 8-PT solution (40 micrograms.kg-1.min-1) produced 95 +/- 3% (P less than 0.001, n = 6) attenuation of exogenous adenosine-induced vasodilation at constant pressure, a 28 +/- 5% (P less than 0.01, n = 6) attenuation of reactive hyperemia, and a 24 +/- 6% (P less than 0.05, n = 6) decrease in hypoxia-induced vasodilation. An 8-PT solution had no effect on systolic segment length shortening and myocardial oxygen consumption. We conclude that 8-PT, when in solution, attenuates but does not abolish the coronary vasodilatory response to hypoxia. Hence, adenosine appears to contribute to hypoxia-induced vasodilation but is not uniquely responsible for the hyperemic response.

Intimal proliferation in coronary arteries of normolipidaemic pigs with a fixed stenosis: the effects of fish oil.

In order to investigate the effect of fish oil on intimal proliferation of coronary arteries with a fixed stenosis, piglets were fed a diet to which either 9% (w/w) lard fat (L, n = 8) or 4.5% (w/w) lard fat and 4.5% (w/w) mackerel oil (ML, n = 8) was added for 4 months. The stenosis was applied by implanting a Teflon constrictor around the left anterior descending coronary artery (LADCA) after the animals had been on their diet for two months. Levels of plasma cholesterol and triglycerides did not change in L, but decreased in ML, while ADP-induced platelet aggregation in whole blood was higher in L than in ML. At the end of the dietary period the animals were anaesthetized and myocardial perfusion and systolic segment length shortening (SLS) were measured while the hearts were paced at 160 pulses min-1. Transmural blood flow to the non-LADCA nourished zones were normal and similar for L and ML, but impaired in the LADCA-perfused myocardium. In particular the subendocardial layers of L were hypoperfused resulting in a larger loss of SLS in L than in ML. A significantly higher encroachment due to intimal proliferation was found in L (62 +/- 7%) than in ML (11 +/- 4%) at the site of the constrictor while this was less than 2% adjacent to the constrictor. We conclude that the presence of the constrictor causes intimal proliferation and that the fish oil-induced changes in platelet aggregation may play a role in determining the extent to which this occurs.

Does platelet aggregation play a role in the reduction in localized intimal proliferation in normolipidemic pigs with fixed coronary artery stenosis fed dietary fish oil?

In order to investigate the effect of fish oil on intimal proliferation of coronary arteries with a fixed stenosis normolipidemic piglets received a basic diet to which either 9% (w/w) lard (L, n = 8) or 4.5% (w/w) lard and 4.5% (w/w) mackerel oil (ML, n = 8) was added for 4 months. Stenosis was applied by implanting a 4.0 × 2.0 mm (i.d.) Teflon constrictor around the left anterior descending coronary artery (LADCA) (o.d. 2.7 ± 0.1 mm). During the dietary period ADP-induced platelet aggregation in whole blood was higher in L than in ML. Partial replacement of 20: 4 n − 6 by 20: 5 n − 3 fatty acids in the platelet membranes of ML may have altered platelet aggregation by changes in eicosanoid synthesis. The plasma cholesterol and triglyceride levels did not change in L, but decreased in ML. At the end of the 4-month dietary period the animals were again anesthetized and regional myocardial perfusion (radioactive labelled microspheres) and systolic segment length shortening (SLS) were measured while the hearts were paced at 160 pulses/min. Perfusion and SLS of the non-LADCA nourished segment were similar for L and ML. However, transmural flow to the LADCA perfused myocardium was impaired in both groups, but the deficiency in endocardial perfusion was considerably larger in L than in ML, resulting in a larger loss of SLS in the former. Remote (2–3 cm from the site of the constrictor) luminal encroachment was minimal (< 2%) in both groups, but at the site of the constrictor there was significant encroachment in both groups which was higher in L (62 ± 7%) than in ML (11 ± 4%). It is thought that in these normolipidemic pigs the reduction in platelet aggregation may play a role in the smaller intimal proliferation of the fish oil-fed animals.