Intravenous magnesium sulphate and reperfused myocardium: preservation of function and reduction of infarct size.

The aim of the study was to examine the effects of intravenous magnesium sulphate (MS) administration on myocardial contractile function and infarct size after occlusion of the left circumflex artery of the heart for 60 minutes. Under sodium pentobarbital anaesthesia (30 mg/kg. intravenously) the hearts of mongrel dogs (n = 13) were instrumented to measure left ventricular pressure (LVP), regional contractile function of the territories perfused by the left circumflex and anterior descending coronary arteries (%SS), mean arterial pressure (MAP), and coronary blood flow velocity (CFV). Immediately upon release of the coronary occlusion, either intravenous magnesium sulphate (100 mg/kg) or a dextrose vehicle (D5W) was infused. Animals were killed, their hearts excised and cut in 1 cm slices from apex to base and incubated in triphenyl tetrazolium chloride (TTC) for 20 minutes to measure infarcted areas. In the control group (n = 7), myocardial contractile function was severely depressed during the occlusion and displayed the same pattern of dysfunction during 3 h of reperfusion. The %SS of the area perfused by the circumflex artery at the end of the reperfusion period was 0.02 +/- 3 (mean + SEM) P < 0.05 vs MS; P < 0.05 vs pre-occlusion) and percentage of necrosis of the area at risk was 17.42 +/- 6 (P < 0.05 vs MS). In the magnesium sulphate group (n = 6), %SS was depressed during the occlusion as in the control group, but was preserved during reperfusion time, 9.8 +/- 1.0 (P < 0.05 vs D5W; P < 0.05 vs pre-occlusion) and showed significantly less percentage of necrotic tissue, 4.53 +/- 1 (P < 0.05 vs D5W). These results suggest that intravenous magnesium sulphate preserves myocardial contractile function and reduces infarct size significantly following a period of complete coronary occlusion.

Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function.

Modulation of myocardial contractile function and perfusion by alpha 1-adrenergic receptors were examined in anesthetized dogs during left stellate ganglion stimulation. In 11 dogs, stellate stimulation significantly increased heart rate, mean arterial pressure, left ventricular systolic pressure, maximal rate of left ventricular pressure generation, segmental shortening and rate of shortening in anterior and posterior ventricular regions, and myocardial oxygen extraction. Myocardial lactate extraction decreased. The selective alpha 1-adrenergic antagonist prazosin (0.5 mg) injected into the circumflex artery during stellate stimulation caused significant additional increases in maximal rate of left ventricular pressure generation by 19 +/- 5% and in rate of shortening in posterior subendocardium by 20 +/- 6%. No changes were observed in posterior subepicardial or anterior subendocardial segmental contractile function. Myocardial oxygen and lactate extractions returned to their control values following prazosin injection. Regional left ventricular perfusion was measured using tracer microspheres in five additional dogs. Stellate stimulation increased subepicardial and subendocardial perfusion by 30%. Prazosin increased both subepicardial and subendocardial perfusion by an additional 36%. Stellate stimulation increased norepinephrine concentration in the coronary sinus, but no further increase was noted after blockage of alpha 1-receptors by prazosin. Thus, during sympathetic stimulation, an alpha 1-vasoconstriction existed uniformly across the left ventricular wall. However, blockade of this vasoconstriction was associated with an increase in contractile function only in the deeper muscle layers.

Endurance training alters arterial baroreflex function in dogs.

The present study was designed to determine whether 12 wk of daily exercise alter autonomic neural control of the heart during baroreflex stimulation in healthy dogs. We studied 16 untrained and 12 endurance-trained anesthetized dogs which were instrumented to measure arterial blood pressure (AP), carotid sinus baroreceptor pressure (CBP), electrocardiogram (ECG), heart rate (HR), and R-R interval (RR). The arterial baroreflex was studied during hypertension caused by i.v. bolus infusion of phenylephrine, hypotension caused by i.v. bolus infusion of nitroprusside, and bilateral carotid occlusion (BCO) in which carotid sinus pressure was reduced to 41 +/- 2 mm Hg (mean +/- SEM). Arterial baroreflex sensitivity, which was assessed by determining the change in heart interval (i.e., change in RR) per unit change in systolic AP (delta RR/delta AP), was significantly lower during the hypertensive challenge in the trained dogs compared to the untrained dogs (2.2 +/- 0.3 vs 6.8 +/- 1.5 ms.mm Hg-1, respectively). Similarly, the delta RR/delta AP was substantially lower during the hypotensive challenge in trained dogs vs the untrained dogs (1.2 +/- 0.3 vs 1.8 +/- 0.4 ms.mm Hg-1, respectively). In addition, the HR response to the BCO was significantly less in trained dogs (22 +/- 2 bpm) vs untrained dogs (32 +/- 5 bpm). The open-loop gain (Go), which was used to quantitate the effectiveness of the carotid baroreflex to increase mean systemic AP during BCO, was similar in both untrained and trained dogs (2.9 +/- 0.6 and 2.4 +/- 0.5, respectively). These data indicate that, while endurance training significantly reduces the HR component of the arterial baroreflex, the arterial pressure response apparently is not altered.

Microvascular occlusions promote coronary collateral growth.

The objective of this study was to examine whether myocardial ischemia without alterations in pressure gradients between large epicardial coronary arteries was a sufficient stimulus to produce coronary collateral growth and development. To accomplish this aim, we partially embolized the circumflex coronary perfusion territory with 25-microns diameter microspheres to produce multiple microvascular occlusions, sufficient to abolish or greatly attenuate coronary vasodilator reserve. The embolization procedure was performed in two groups of dogs during aseptic surgery. After the dogs recovered for 1-3 wk (short-term embolization) or 6-8 wk (long-term embolization), indexes of vascular growth were compared with a group of control animals in which all operative procedures were performed, except embolization. Retrograde blood flow, an index of collateral blood flow and coronary vascular resistance, was determined in an isolated beating empty heart preparation during coronary vasodilation with adenosine. Circumflex retrograde blood flow from the left anterior descending artery was increased from 0.09 ml.min-1.g-1 (sham) to 0.21 and 0.17 ml.min-1.g-1 in the short-term and long-term groups, respectively (P less than 0.05). Collateral blood flow from the septal artery was also increased from 0.03 ml.min-1.g-1 (sham) to 0.08 ml.min-1.g-1 (P less than 0.05) in the short-term group. Collateral contribution from the right coronary artery was not significantly altered in either group of embolization animals. The contributions of epicardial and intramyocardial collaterals to the total retrograde flow were also determined and were found to be different among the three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramural coronary collateral flow in dogs.

The objective of this study was to determine whether intramural collaterals contribute significantly to total retrograde flow (index of collateral flow). The left circumflex, left anterior descending, right, and septal coronary arteries were separately cannulated, and blood flows through these vessels were monitored on an isolated, blood-perfused beating heart preparation. Epicardial collaterals between the borders of the circumflex and right coronary perfusion territories were cauterized, and retrograde flow from the circumflex coronary artery was determined before and after cauterization. This procedure unmasked the intramural collateral flow component to retrograde flow. By occluding and unoccluding the coronary flows from the right, septal, and left anterior descending coronary arteries during these measurements, we were able to determine their contribution to epicardial and intramural collateral flow. We found that, after cauterization, an average of 58 +/- 3.6% of the total retrograde flow remained. The septal and left anterior descending coronary arteries contributed almost equally to this retrograde flow. We concluded that, because the epicardial collaterals were cauterized, the source of retrograde flow was from intramural collaterals and constituted about one-half of the measured retrograde flow in dogs with a native collateral circulation.

Coronary and cardiac responses to exercise after chronic ventricular sympathectomy.

This study examined the effects of chronic surgical ventricular sympathectomy on the relationships between left ventricular mechanical performance, coronary blood flow, and exercise workload in sham-operated control dogs and dogs which had been ventricular sympathectomized 8 wk earlier. During exercise, left ventricular global contractile state was less in sympathectomized ventricles than in control ventricles, as indicated by reduced systolic pressure and maximal rate of pressure generation. Regional contractile shortening was not different. Heart rate was significantly elevated in sympathectomized ventricles. Therefore, peak systolic pressure-heart rate product and tension-time index were not different in sympathectomized ventricles compared to control ventricles. However, at each level of exercise, mean coronary flow in sympathectomized ventricles was reduced by about 50% compared to control values. The slopes of coronary flow on pressure-rate product and tension-time index were also reduced. No difference in left ventricular oxygen extraction between control and sympathectomized hearts were observed. Thus, chronic ventricular sympathectomy altered the relationships between coronary flow and oxygen consumption, on the one hand, and ventricular oxygen-dependent performance and whole-body exercise level, on the other hand.

Response to brief coronary stenosis in conscious dogs after ventricular sympathectomy.

Left ventricular responses to 2-min circumflex occlusion were studied in conscious dogs. In nonsympathectomized controls at 2, 4, and 8 wk after surgery for cardiac instrumentation, segmental shortening in the posterior ventricle significantly decreased by 111, 87, and 81% of the preocclusion values, respectively (P less than 0.05). The decrease in shortening was associated with increases in end-diastolic pressure of 9, 9, and 8 mmHg (P less than 0.05), decreases in the maximal rate of pressure generation of 305, 272, and 340 mmHg/s (P less than 0.05), and increases in heart rate of 28, 21, and 20 beats/min, respectively (P less than 0.05). After 2 and 4 wk of ventricular sympathectomy, posterior segmental shortening declined by 38 and 31%, respectively (P less than 0.05), but these decreases were less than in controls (P less than 0.05). Shortening did not change during occlusion after 8 wk of sympathectomy. Diastolic pressure increased by 6 mmHg (P less than 0.05), and the rate of pressure generation decreased by 232 mmHg/s (P less than 0.05) in the 2-wk sympathectomized ventricle. These variables did not change significantly after 4 and 8 wk of sympathectomy. After 2, 4, and 8 wk of sympathectomy, the increases in heart rate during circumflex occlusion were not different from controls (P greater than 0.05). Thus chronic sympathectomy preserved ventricular function during occlusion. This effect was attributable to a reduced preocclusion mechanical performance with a reduction in blood flow requirement and to an increased collateral perfusion, as indicated by a higher peripheral coronary pressure during occlusion in sympathectomized ventricles.

Computer analysis of cardiovascular parameters.

A computer program is described for the analysis of several cardiovascular parameters frequently measured or derived in the chronically instrumented dog model. Data are stored on magnetic tape and are subsequently analyzed with the Apple IIe microcomputer equipped with the ADALAB (Interactive Microware, Inc.) analog-to-digital convertor. Not limited to the chronically instrumented animal model, the program is capable of analyzing left ventricular pressure, three channels of regional myocardial segment length, coronary flow velocity as measured by the Doppler ultrasonic flow technique, and two channels of systemic arterial pressure. Derived data include: left ventricular dP/dtmax, left ventricular pressure-heart rate product, left ventricular ejection time, tension time index; percent segment length shortening and velocity of shortening, dL/dt(s)max, regional stroke work and power, duration of systole and diastole; mean coronary flow velocity, peak diastolic and systolic flow velocity, and true mean systemic arterial pressure.

Modulation of synchrony of left ventricular contraction by regional adrenergic stimulation in conscious dogs.

The sympathetic innervation of the left ventricle provides a potential mechanism for modulation of synchrony of myocardial contraction. Dogs were instrumented to measure left ventricular pressure and segment length in the posterior region of the left ventricle perfused by the circumflex artery (PSL) and in an anterior region perfused by the anterior descending artery (ASL). Norepinephrine (NE) was injected into the circumflex artery using an indwelling catheter in bolus doses sufficient to produce no direct systemic effects. Intracoronary injection of NE resulted in significant increases in percent segment shortening and mean shortening velocity in the PSL. Duration of shortening in the PSL was significantly reduced. Percent shortening, velocity of shortening, and shortening duration in the ASL were unchanged. While there was no change in left ventricular systolic pressure, +dP/dtmax and -dP/dt min increased with intracoronary NE. These results demonstrate alterations in the synchrony of myocardial contraction following regional myocardial stimulation with intracoronary injections of NE at doses within the expected physiological range and suggest that activation of localized sympathetic neural pathways may result in problems involving mechanical performance of the heart.

Alpha 1-adrenergic constriction limits coronary flow and cardiac function in running dogs.

Modulation of coronary blood flow and cardiac function by alpha 1-adrenergic receptors was examined in dogs during strenuous exercise. Fifteen dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function (systolic shortening, and rate of shortening), and global left ventricular function (left ventricular pressure, and dP/dt). The specific postsynaptic alpha 1-receptor blocker prazosin (0.5 mg) and nonselective alpha-receptor blocker phentolamine (1.0 mg) were injected through an indwelling circumflex artery catheter to produce local adrenergic blockade of the posterior left ventricular region during exercise. Exercise significantly increased heart rate, left ventricular systolic pressure, dP/dt, segment shortening and rate of shortening, and coronary blood flow. Both prazosin and phentolamine caused similar additional increases in dP/dt by 21 +/- 4%, in rate of shortening in the posterior region by 37 +/- 6%, and in myocardial O2 consumption by 26 +/- 11%, which were associated with a 21 +/- 3% increase in coronary flow during exercise but no change in O2 extraction. Similar results were obtained when dogs were beta-blocked with either atenolol (1.0 mg ic) or propranolol (1.0 mg ic) prior to exercise. These data suggest that an alpha 1-vasoconstriction modulates O2 delivery to myocardial tissue and limits both coronary vasodilation and cardiac function during exercise.