Myocardial Ischemia In Conscious Dogs Research Articles

Viscerosomatic interaction induced by myocardial ischemia in conscious dogs

Studies tested the hypothesis that myocardial ischemia induces increased paraspinal muscular tone localized to the T(2)-T(5) region that can be detected by palpatory means. This is consistent with theories of manual medicine suggesting that disturbances in visceral organ physiology can cause increases in skeletal muscle tone in specific muscle groups. Clinical studies in manual and traditional medicine suggest this phenomenon occurs during episodes of myocardial ischemia and may have diagnostic potential. However, there is little direct evidence of a cardiac-somatic mechanism to explain these findings. Chronically instrumented dogs [12 neurally intact and 3 following selective left ventricular (LV) sympathectomy] were examined before, during, and after myocardial ischemia. Circumflex blood flow (CBF), left ventricular contractile function, electromyographic (EMG) analysis, and blinded manual palpatory assessments (MPA) of tissue over the transverse spinal processes at segments T(2)-T(5) and T(11)-T(12) (control) were performed. Myocardial ischemia was associated with a decrease in myocardial contractile function and an increase in heart rate. MPA revealed increases in muscle tension and texture/firmness during ischemia in the T(2)-T(5) segments on the left, but not on the right or in control segments. EMG demonstrated increased amplitude for the T(4)-T(5) segments. After LV sympathectomy, MPA and EMG evidence of increased muscle tone were absent. In conclusion, myocardial ischemia is associated with significant increased paraspinal muscle tone localized to the left side T(4)-T(5) myotomes in neurally intact dogs. LV sympathectomy eliminates the somatic response, suggesting that sympathetic neural traffic between the heart and somatic musculature may function as the mechanism for the interaction.

Left ventricular systolic dysfunction precedes diastolic dysfunction during myocardial ischemia in conscious dogs.

We studied the initial effects of regional and global left ventricular (LV) ischemia induced by left circumflex and left main coronary artery occlusion (CAO), respectively, on indexes of systolic and diastolic LV function in conscious dogs to determine whether diastolic abnormalities precede systolic dysfunction or vice versa during the onset of either regional or global myocardial ischemia. With regional myocardial ischemia, within four beats after left circumflex CAO, there was a significant decrease in end-systolic wall thickness in the ischemic zone followed by significantly enhanced postsystolic wall thickening in the nonischemic zone at beat 6. Both peak negative first derivative of left ventricular pressure (LV dP/dt) and the isovolumic relaxation half-time (T 1/2) were prolonged, but later (i.e., by the 9th beat). During sustained CAO T1/2 was normalized shortly after postsystolic thickening in the nonischemic zone had disappeared despite persistent regional systolic asynchrony and shortened ejection time. Thus postsystolic thickening in the nonischemic zone played a major role in the early, transient changes in isovolumic relaxation after acute induction of regional ischemia. With global myocardial ischemia, induced by left main coronary occlusion, indexes of systolic function (e.g., LV dP/dt, ejection fraction, and velocity of circumferential endocardial fiber shortening) were also depressed significantly before (by 5-15 beats) indexes of LV diastolic function [e.g., time constant of isovolumic relaxation and LV myocardial and chamber stiffness (by 35-45 beats)]. Similar results were observed in the presence of autonomic blockade, when heart rate did not change with CAO. Thus, during the induction of either acute regional or acute global LV ischemia in conscious dogs, LV systolic dysfunction occurs before diastolic dysfunction.

Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction

The role of vagal tone and reflexes in the genesis of life-threatening arrhythmias was investigated in a clinically relevant animal model for sudden cardiac death. Forty-five dogs with a healed anterior myocardial infarction in which transient myocardial ischemia during exercise did not induce malignant arrhythmias were utilized for the study. They underwent a further exercise and ischemia test in which atropine (75 micrograms/kg) was injected before coronary artery occlusion. Novel occurrence of ventricular arrhythmia, or worsening of the type of arrhythmia present in the control test, occurred in 23 of 45 dogs (51%) and ventricular fibrillation occurred in 11 of 45 (24%, P = 0.001). Analysis of heart rate response to acute ischemia in the control test indicates that these 11 animals had powerful vagal reflexes during coronary artery occlusion, compared with the 34 survivors (-32 +/- 35 vs. +2 +/- 27 beats/min, P = 0.003). This study indicates that approximately 75% of animals resistant to ventricular fibrillation are characterized by weak sympathetic reflexes in response to acute myocardial ischemia. In the remaining 25% powerful vagal reflexes counteract concomitant reflex sympathetic hyperactivity, decrease heart rate, and are essential for survival.

One hour of myocardial ischemia in conscious dogs increases β-adrenergic receptors, but decreases adenylate cyclase activity

An increased myocardial beta-adrenergic receptor density has been reported following myocardial ischemia. However, it is not clear whether these receptors are effectively coupled to adenylate cyclase which would be necessary for enhanced physiological responsiveness. We, therefore, examined the effects of myocardial ischemia in six conscious dogs (4 intact and 2 with posterior wall denervation) in which the left circumflex coronary artery was occluded. Ischemia was verified by measurement of regional blood flow by radioactive microspheres. After 1 h of coronary artery occlusion, the dogs were anesthetized with pentobarbital and the left ventricle was divided into normal, intermediate and ischemic regions. A crude membrane fraction was prepared from each region. beta-Adrenergic receptors were quantitated with 125I-cyanopindolol binding and adenylate cyclase activity was measured. In all six animals studied, beta-adrenergic receptor density increased progressively and adenylate cyclase activity decreased progressively, when the ischemic myocardium was compared to the intermediate and the non-ischemic myocardium. Since adenylate cyclase activity declined, these results do not support the concept that the increased beta-receptor density induced by myocardial ischemia is causally related to enhanced beta-adrenergic sensitivity.

Characterization of nonischemic segment shortening during variable extent of myocardial ischemia in conscious dogs.

Studies were performed on seven conscious dogs chronically instrumented for measurement of subendocardial segment length in the central area perfused by the left circumflex coronary artery (LCCA) and left anterior descending coronary artery, LCCA flow, and left ventricular pressure. We occluded the LCCA for 2 min using an externally inflatable pneumatic occluder placed around the proximal LCCA. Two-minute LCCA occlusions were repeated hourly for 8 h, 5 days/week. The first LCCA occlusion decreased the ejection phase shortening in the ischemic area from 22.2% +/- 2.5% (SEM) to 3.1% +/- 0.7% (P less than 0.001). Concomitantly, heart rate increased from a resting rate of 76 +/- 4 to 117 +/- 6 beats/min (P less than 0.001) after 2 min of LCCA occlusion, and ejection phase shortening in the nonischemic area decreased from 25.5% +/- 1.3% to 21.6% +/- 1.1% (P less than 0.001) despite increases in end-diastolic segment length (15.31 +/- 1.46 mm to 15.69 +/- 1.52 mm, P less than 0.01). These changes in non-ischemic segment shortening and heart rate during LCCA occlusion were attenuated progressively with improvement tin the regional myocardial function at jeopardy due to the development of collateral circulation, and a significant (P less than 0.001) correlation between both the reduced nonischemic segment shortening and the increased heart rate with the degree of dysfunction in the ischemic region was obtained by linear regression analysis with Fisher's Z transformation.

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.

We examined the importance of decreased heart rate in the beneficial effect of beta-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3-1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 +/- 25 beats per minute (SD, n = 9) to 166 +/- 15, and ischemic zone wall thickening during systole improved from 27 +/- 22% of the resting value in the control run to 50 +/- 25% of the resting value in the atenolol run (p less than 0.01). Atrial pacing then increased heart rate to 217 +/- 23 beats per minute, and regional wall thickening deteriorated to 15 +/- 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

The effect of combination therapy with diltiazem and atenolol on the regional myocardial blood flow-function relationship was studied in eight conscious dogs with chronic coronary artery stenosis. An ameroid constrictor and hydraulic occluder were placed around the left circumflex coronary artery, sonomicrometers were implanted for measuring wall thickness in control and ischemic regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery, resting regional myocardial function and blood flow were normal, but treadmill exercise induced severe regional myocardial dysfunction in the posterior wall (wall thickening during systole reduced from 25.5% to 2.7%, a 90% reduction). Subendocardial blood flow decreased by 68% from the control standing value, while subepicardial flow increased. An identical exercise bout was performed 3 hr after administration of atenolol (1.0 mg/kg orally) and 15 min after administration of diltiazem (0.3 mg/kg iv). Heart rate during running was significantly lower as were left ventricular peak systolic pressure, end-diastolic pressure, and peak dP/dt. Wall thickening in the control region was not augmented during exercise after atenolol and diltiazem. There was less dysfunction in the ischemic region (35% reduction) and the improved performance was accompanied by a substantial increase in subendocardial perfusion (0.31 +/- 0.14 vs 0.61 +/- 0.30 ml/min/g, a 36% reduction from rest). Epicardial flow was unchanged, and the endocardial/epicardial ratio increased (0.27 +/- 0.13 vs 0.62 +/- 0.29). Recovery time for regional wall thickening also improved. The beneficial effects of the combination of atenolol and diltiazem in a preparation of single-vessel chronic coronary stenosis were shown to be significantly greater than those of either drug alone.

End-systolic dimension-wall thickness relations during myocardial ischemia in conscious dogs: A new approach for defining regional function

Overall and regional left ventricular (LV) function was studied during progressive coronary stenosis in conscious dogs by determining the relations at end-systole between LV pressure, chamber dimensions, and regional LV wall thickness. An index of regional wall stress was also analyzed. Using ultrasonic dimension gauges, measurements were made of LV wall thickness in control and ischemic regions, and the external long- and short-axis LV diameters were determined; an implanted micromanometer measured LV pressure. Internal LV diameters were obtained from the external diameters by subtraction of wall thickness, and the index of regional wall stress employed a thick-walled ellipsoidal model. During regional ischemia, the LV long axis at end-systole did not change, whereas the short-axis diameter progressively increased (from 24 ± 7 mm [standard deviation] to 30 ± 9 mm, p < 0.001, indicating a more spherical LV shape during ischemia). The end-systolic pressure did not change, and therefore the end-systolic pressure-diameter relation shifted progressively, suggesting a global decrease in LV contactility. The end-systolic points relating LV wall thickness in the ischemic region to the end-systolic LV pressure revealed the regional nature of the abnormality, showing a progressive displacement to the left, whereas there was no significant displacement of this relation in the control region. The application of this index over a range of loading conditions during partial vena caval occlusion was illustrated. Thus, the regional endsystolic wall thickness-pressure relation provides a new index for defining the regional contractile state of the LV myocardium which is potentially load-independent and offers the possibility for echocardiographic application.

Left stellectomy in the prevention of ventricular fibrillation caused by acute myocardial ischemia in conscious dogs with anterior myocardial infarction.

The potential of left stellectomy in reducing the incidence of ventricular fibrillation associated with acute myocardial ischemia was investigated in a new animal model for sudden death. Thirty-two dogs had an anterior myocardial infarction produced by ligation of the left descending coronary artery. One week later they were randomly allocated to a control or to an experimental group that underwent left stellectomy. One month after ligation while the dogs were conscious, a balloon occluder previously positioned around the circumflex coronary artery was inflated and the ensuing coronary occlusion was maintained for 10 minutes. Ventricular fibrillation occurred in 11 of 17 (65%) control dogs, compared with five of 15 (33%) (p < 0.05) in the experimental group. Among the survivors the incidence of arrhythmias was less in the experimental group compared with the control group. Infarct size (21 +/- 2% vs 20 +/- 2%), resting heart rate (143 beats/min vs 127 beats/min) and QTc (347 +/- 11 msec vs 349 +/- 13 msec) were similar between control and experimental groups. The dogs that died had a greater increase in heart rate at 1 minute postocclusion than survivors and also had significantly longer QT intervals. Our study indicates that left stellectomy exerts a major protective effect in reducing the incidence of ventricular fibrillation when conscious dogs with a previous anterior myocardial infarction undergo acute myocardial ischemia. This simple and safe surgical procedure may be considered for a clinical trial in subgroups of patients with ischemic heart disease at very high risk for sudden death.