Systolic Segment Shortening Research Articles

Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation

After brief coronary occlusions, myocardium may become "stunned," exhibiting prolonged depression of function despite the absence of necrosis. Because of the accompanying decline in adenosine triphosphate and adenine nucleotide precursors, a deficiency of energy supply has been proposed as the basis for postischemic dysfunction. This study examined whether sufficient functional and metabolic reserve exists in stunned myocardium to sustain a prolonged, maximal inotropic response to epinephrine and postextrasystolic potentiation. In 11 open chest dogs, the left anterior descending coronary artery was occluded for 5 minutes, followed by 10 minutes of reflow, repeated 12 times, with a final 1 hour recovery period. Regional myocardial function was measured using pairs of ultrasonic dimension crystals implanted in ischemic and nonischemic zones. During repetitive reflows a progressive decrease in mean systolic segment shortening occurred: baseline 21.8%, 1st reflow 15.2%, 12th reflow 4.3%, 1 hour recovery 7.9%. Intravenous epinephrine, titrated to produce a maximal inotropic response, caused segment shortening to increase to 21.6% after 10 minutes and to 24.8% after 1 hour of infusion, despite a 20 mm Hg increase in systolic pressure. The same dose of epinephrine given before ischemia increased segment shortening to 30.5%. In six of the dogs, postextrasystolic potentiation before ischemia increased segment shortening from 21.8 to 31.1%, and after 1 hour of recovery from ischemia, from 7.9 to 24.8%. Lesser increases in segment shortening were also seen in nonischemic segments. The results indicate that stunned myocardium possesses considerable functional reserve. Deficient energy stores are therefore not likely to be the basis for depressed function seen at rest in stunned myocardium.

The changes in ECG ST segment and mechanical function of regional ischemic myocardium during afterload reduction in isolated dog hearts with coronary stenosis.

By measuring ECG ST segment deviation and regional mechanical dysfunction, we assessed the effects of an alteration in afterload pressure on regional myocardial ischemia due to a partial coronary occlusion of the left circumflex coronary artery (CFX). Eight isolated, perfused and paced dog hearts were loaded with an artificial arterial system which simulated the aortic input impedance of the dog arterial tree. Afterload pressure was altered by stepwise changes in peripheral resistance (Rp), while left ventricular end-diastolic pressure (LVEDP) and heart rate were kept constant. Coronary perfusion pressure (CPP) was kept equal to mean aortic pressure (AoP). ECG and myocardial systolic segment shortening (SS) were measured in both areas perfused by the CFX and the left anterior descending coronary artery (LAD). In the presence of CFX stenosis, mean AoP decreased from 96 +/- 7 to 46 +/- 7 mmHg following a decrease in Rp and cardiac output increased progressively from 465 +/- 30 to 1055 +/- 100 ml/min. In this situation, CFX coronary blood flow decreased from 75 +/- 2 to 28 +/- 6 ml/100 g/min. Epicardial ECG in the ischemic region showed two types of ST segment deviation after CFX stenosis: ST segment elevation and ST segment depression. Moreover, following afterload reduction, these individual ECG ST segment changes showed further deviations. The levels of mean AoP, below which further ST segment deviations significantly occurred, were as follows: 71 +/- 6 mmHg in ST segment elevation cases and 52 +/- 7 mmHg in ST segment depression cases. Myocardial systolic segment shortening in the ischemic region also significantly decreased following CFX stenosis (91 +/- 8% of pre-ischemic control, p less than 0.05). Then, during afterload reduction, SS in the CFX area appeared to be bimodal and it definitely decreased when mean AoP was 46 +/- 7 mmHg. To enhance the sensitivity of detection of further mechanical dysfunction throughout afterload reduction following regional myocardial ischemia, we calculated percentage values of the SS in the CFX area to the SS in the LAD area at each Rp. By this normalization, mechanical dysfunction was found when mean AoP was below 67 +/- 5 mmHg. These results suggest that reduction in afterload pressure below a certain level aggravated the regional ischemia, despite an increase in cardiac output, and to detect this change in the ischemic region during afterload reduction, ECG ST segment deviation seems to be a useful indicator.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of OPC-8212, a New Positive Inotropic Agent, and Dobutamine on Left Ventricular Global and Ischemic Regional Functions and Coronary Hemodynamics Under Coronary Artery Stenosis

We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of control flow). OPC-8212 infusion (n = 7) under LCX stenosis improved cardiac depression [i.e., peak LV dP/dt increased from 1,295 +/- 143 mm Hg/s to 2,669 +/- 266 mm Hg/s (mean +/- SEM) (p less than 0.001)], while myocardial ischemic injury, assessed by myocardial CO2-tension and electrocardiogram (ECG)-ST changes, improved (i.e., delta CO2-tension and ECG-ST deviation decreased from 21.1 +/- 3.6 mm Hg and 3.8 +/- 0.6 mV to 13.3 +/- 2.8 mm Hg (p less than 0.01) and 2.0 +/- 0.7 mV (p less than 0.05), respectively). On the other hand, dobutamine infusion (n = 7) further increased myocardial CO2-tension and ECG-ST deviation [i.e., delta CO2-tension and ECG-ST deviation increased from 14.4 +/- 4.2 mm Hg and 2.5 +/- 1.2 mV to 29.0 +/- 6.0 mm Hg (p less than 0.01) and 4.9 +/- 1.0 mV (p less than 0.01), respectively]. At the same time, peak LV dP/dt clearly improved, but to a lesser degree; from 1,425 +/- 153 mm Hg/s to 2,393 +/- 245 mm Hg/s (p less than 0.001). There was also an increase in percent systolic segment shortening of each corresponding area as with OPC-8212.(ABSTRACT TRUNCATED AT 250 WORDS)

EVIDENCE AGAINST THE ADENOSINE-CATECHOL AMINE ANTAGONISM IN THE IN SITU DOG HEART: 183

Adenosine has been reported to attenuate the positive inotropic effects of catecholamines in in vitro-heart preparations of rodents. These results were not confirmed in anesthetized dogs during intracoronary infusion of isoproterenol. However, these experiments did not study the effects of adenosine on the inotropic effects of endogenously released catecholamines. Therefore we performed cardiac sympathetic nerve stimulation (CSNS) in 5 anesthetized, vagotomized dogs. The left circumflex coronary artery was perfused at a constant pressure of 130±4 mmHg. The contractile function of the circumflex-perfused myocardium was analyzed by sonomicrometry. CSNS at 1, 2, 5, 10 and 20 Hz increased systolic segment shortening (SScx) in a frequency-dependent manner from 10.9±2.6 at control to 15.3±3.4 % at 20 Hz. During intracoronary infusion of adenosine (50 μg/ kg/min) CSNS still increased SSCX frequency-dependently from 9.9±3.5 to 16.3±4.5 %. The lack of any adenosine-catecholamine antagonism in our experiments was not due to the sequence of procedures, nor to the marked flow increase induced by adenosine, since SSCX at rest was rather reduced with adenosine infusion and since during intracoronary infusion of papaverine and sodium-nitroprusside similar results were obtained. It seems that the observation of adenosine-catecholamine antagonism in rodents is a species dependent phenomenon. Supported by SFB 30 - Kardiologie, Dusseldorf

Effects of coronary artery reperfusion on regional myocardial blood flow and function in conscious baboons.

The effects of coronary artery reperfusion initiated 1 hr and 3 hr after coronary artery occlusion were evaluated on measurements of overall and regional left ventricular function and on regional myocardial blood flow. These experiments were conducted in conscious baboons 2 to 3 weeks after recovery from instrumentation with a solid state left ventricular pressure gauge, aortic and left atrial catheters, a hydraulic occluder around the mid left anterior descending coronary artery, and pairs of ultrasonic transducers implanted in the endocardium of the left ventricular free wall or across the free wall to measure endocardial segment shortening and wall thickening, respectively. Coronary artery occlusion induced similar effects in both groups. At 1 hr after occlusion, the ischemic zone was characterized by severe and equal reductions in both endocardial (-97 +/- 1%) and epicardial (-95 +/- 4%) blood flows and complete loss of regional systolic function, which was replaced by paradoxical wall motion. Reperfusion initiated after 1 hr of ischemia was associated with a marked transient increase in endocardial (+386 +/- 51%) and epicardial (+544 +/- 79%) blood flows. During the subsequent 4 weeks, segment shortening and wall thickening tended to improve. However, at 4 weeks after reperfusion, segment shortening was still depressed by 45 +/- 12% and wall thickening by 58 +/- 14%. In contrast, reperfusion initiated after 3 hr of ischemia was not associated with a significant hyperemic response, and systolic segment shortening and wall thickening did not recover during the subsequent 4 week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Intracoronary Nifedipine on Blood Flow and Segment Shortening in Normal and Ischemic Myocardium

The effects of intracoronary nifedipine on myocardial blood flow (flow probe or microspheres) and regional function (ultrasonic crystals in subendocardium) were examined both in the normal myocardium and in myocardium made ischemic by a partial coronary occlusion in the open-chest anesthetized dog. In a first group of experiments (n = 7), without ischemia, nifedipine infused into the left anterior descending coronary artery (LAD) during a 1-min period (doses 0.75-8 nmol/kg body weight) decreased coronary vascular resistance with a maximal effect at 4 nmol/kg. Systolic segment shortening was decreased from 10.7 to 7.4% (p less than 0.05) by 6 nmol/kg, whereas lower doses had no effect. In a second experimental group (n = 7), a partial LAD occlusion was applied to decrease subendocardial segment shortening by about 50%. Nifedipine (2 nmol/kg) injected into the partially occluded LAD induced a marked segmental bulging during early systole and systolic segment shortening was eliminated (from 4.2 to -3.1%, p less than 0.02) in the LAD-dependent myocardium. Concomitant with the decreased regional function, nifedipine caused a transmural redistribution of myocardial blood flow in the ischemic area, the endocardial/epicardial blood flow ratio increasing from 0.49 to 0.61 (p less than 0.02). It is concluded that ischemia potentiates the direct depressant effect of nifedipine on myocardial regional function.

Prostaglandin E1 increases myocardial contractility in the conscious dog.

The systemic and inotropic properties of prostaglandin E1 (PGE1) were investigated in 20 unanesthetized dogs. Pairs of ultrasonic dimension gauges and a micromanometer were implanted in the subendocardium and the apex of the left ventricle (LV), respectively. Seven to ten days later, increasing doses of PGE1 were infused into the left atrium. To appreciate the inotropic effects of the agent, the heart rate was maintained constant at 150 beats/min in a subgroup of dogs while preload was modified by bleeding or saline infusion over matched ranges of end-diastolic segmental length (EDL) during placebo and PGE1 infusions (0.25 microgram . kg-1 . min-1). LV function curves (delta L: systolic segmental shortening versus EDL) were plotted. Increasing doses of PGE1 above 0.031 microgram . kg-1 . min-1 brought a progressive decrease of left ventricular end-diastolic pressure, EDL, delta L, and peak left ventricular systolic pressure. The heart rate increased significantly at dosages from 0.063 to 0.125 microgram . kg-1 . min-1, and peak positive dP/dt after an initial increase fell at the dose of 0.5 microgram . kg-1 . min-1. The LV function curves invariably showed a shift to the left when PGE1 was administered; as the basal EDL was restored during PGE1 infusion, delta L reached a 33% increase (p less than 0.001). Thus, in addition to its potent vasodilating properties that are more prominent on preload than afterload, PGE1 increases myocardial contractility in the conscious dog.

Nifedipine prevents sympathetic vasoconstriction distal to severe coronary stenoses.

Cardiac sympathetic nerve stimulation ( CSNS ) can induce vasoconstriction distal to severe coronary stenoses by activation of vascular alpha 2-adrenoceptors. Whether nifedipine can antagonize this CSNS -induced vasoconstriction was tested in 11 anesthetized, vagotomized dogs. CSNS decreased the end-diastolic resistance of intact coronary arteries from 0.76 +/- 0.07 to 0.56 +/- 0.05 mm Hg x min x 100 g/ml (p less than 0.05). In contrast, the resistance distal to severe stenoses, which were defined by a reduction of the postocclusive reactive hyperemia to almost zero, was increased during CSNS from 0.52 +/- 0.06 to 0.87 +/- 0.14 mm Hg x min x 100 g/ml (p less than 0.05). This increase in resistance was associated with severe ischemia, as indicated by a net lactate production of the circumflex-perfused myocardium and a decrease in systolic segment shortening from 8.4 +/- 0.7 to 7.0 +/- 0.7% (p less than 0.05). Both intracoronary (10 micrograms) and intravenous (10 micrograms/kg) administration of nifedipine did not change the poststenotic resistance at rest, but did prevent the CSNS -induced increase in resistance, the decrease in regional contraction, and the net lactate production. We conclude that nifedipine can prevent the deleterious role of alpha-adrenoceptor-mediated vasoconstriction in the genesis of myocardial ischemia.