Nonischemic Segments Research Articles

Effects of nisoldipine on recovery of coronary blood flow, sarcoplasmic reticulum function and other biochemical parameters in post-ischaemic porcine myocardium

The effects of nisoldipine (0.1 μg/kg/min; n = 9) or its solvent ( n = 9) were studied in pigs, in which left anterior descending coronary artery (LADCA) blood flow in both groups was reduced to 20% of baseline for 60 min and reperfused for 2 hr. Infusions were started at 30 min of ischaemia and lasted throughout reperfusion. In both groups, flow reduction abolished regional contractile function and caused similar decreases in the level of creatine phosphate (CP; by 70%) and the energy charge (from 0.91 to 0.69), mean arterial blood pressure (by 25%), LVdP/d t max (by 30%) and cardiac output (by 30%). During ischaemia LADCA blood flow slightly increased (from 14 ± 8 to 24 ± 6mL/min/ 100 g; P < 0.05) in the nisoldipine-treated animals, resulting in an increase in CP to 91 ± 24% of baseline and preventing further decreases in energy charge, as observed in the solvent-treated animals. After 2 hr of reperfusion in neither group return of contractile function of the post-ischaemic myocardium was observed. Post-ischaemic blood flow in the nisoldipine-treated pigs increased from 24 ± 6 mL/min/100 g to 76 ± 14 mL/min/100 g and from 19 ± 6 mL/min/100 g to 41 ± 6 mL/min/100 g in the solvent-treated animals (P < 0.05) after 2 hr of reperfusion. Myocardial work was significantly higher in the nisoldipinetreated animals (111 ± 15 mmHg.L/min as compared to 69 ± 14 mmHg.L/min in the solvent-treated pigs after 2 hr of ischaemia). The energy charge of the post-ischaemic myocardium was similar for both groups (0.84 ± 0.02 for the nisoldipine-treated and 0.83 ± 0.03 for the solvent-treated animals). The rate of sarcoplasmic reticular Ca 2+ uptake of the non-ischaemic segment of the nisoldipine-treated animals was 61% higher (P < 0.05) than that of the solvent-treated animals. In the post-ischaemic myocardium similar rates of Ca 2+ uptake were found in both groups, but the activities were markedly lower as compared to the non-ischaemic myocardium. It is concluded that nisoldipine increases blood flow during reperfusion, which may have been caused by coronary vasodilatation. However, attenuation of the “no-reflow” phenomenon also contributed, since more rapid rephosphorylation of ADP leading to an increase in CP during ischaemia may have preserved jeopardized cells. Moreover, nisoldipine increases the sarcoplasmic reticular Ca 2+ pump activity independent of ischaemia, which may have contributed in reducing the Ca 2+ overload.

Left ventricular pressure-length relation during exercise-induced ischemia

The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise-induced deterioration in wall motion was used as an intrapatient control (nonischemic segment).In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p < 0.001), end-diastolic pressure increased (from 24 to 40 mm Hg, p < 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p < 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p < 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p < 0.01). Global left ventricular diastolic pressure-volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise. Regional stiffness increased during exercise-induced ischemia in the ischemic but not in the nonischemic segment.In conclusion, the global left ventricular diastolic pressure-volume relation shows an upward and rightward shift during exercise-induced ischemia, whereas the regional pressure-length curves of the nonischemic and ischemic segments show an upward shift only during early, but not during late, diastole. This early diastolic upward shift of the regional pressure-length curve is more pronounced in the nonischemic segment. Regional stiffness is increased only in the ischemic segment. Thus, there is a time-dependent upward shift of the regional pressure-length curve during exercise-induced ischemia that is probably due to delayed relaxation in the ischemic segment and increased viscous forces in the nonischemic segment.

Effects of nifedipine on left ventricular distensibility, relaxation and filling dynamics during pacing-induced myocardial ischemia

Diastolic left ventricular properties were assessed in 8 patients with coronary artery disease at rest and during postpacing states before and after nifedipine (10 mg sublingually). Typical anginal pain developed in all patients during pacing tachycardia before but not after nifedipine. Postpacing increases in end-diastolic pressure (10 ± 5 [mean ± standard deviation]to 23 ± 9 mm Hg) and volume (99 ± 29 to 113 ± 27 ml) were greatly attenuated with nifedipine (13 ± 7 and 97 ± 22 ml, respectively). These responses were associated with normalization of postpacing shifts of the ventricular diastolic pressure-volume curve upward or more to the right. The time constant of ventricular relaxation was prolonged by pacing tachycardia (44 ± 10 to 62 ± 5 ms) and was reduced to the control level in postpacing beats after nifedipine. The peak rate of early ventricular filling was affected neither by pacing stress nor by nifedipine. When regional myocardial function was expressed by a radial coordinate system, the nonischemic segment responded to the control pacing with an increase in end-diastolic length and comparable augmentation of the stroke excursion, while the ischemic segment showed a marked reduction in stroke excursion with end-diastolic length unchanged. Thus, the diastolic pressure-length relation moved up to the higher portion of the single curve in the nonischemic segment, while it shifted directly upward in the ischemic segment. These responses were markedly attenuated with nifedipine. The peak rate of segmental lengthening increased in postpacing beats before and after nifedipine in the normal segment, while it decreased by pacing stress with significant improvement with nifedipine in the ischemic segment. Thus, the net global changes in left ventricular diastolic function are determined by the complex interaction of changes in the regional myocardium, and favorable effects of nifedipine on global responses to transient ischemia are largely mediated by selective improvement of the ischemic segment.

Alterations in left ventricular relaxation, early diastolic filling and passive viscoelastic properties during postpacing ischemia

Alterations in left ventricular relaxation, early diastolic filling, regional myocardial dynamics and passive viscoelastic properties during postpacing ischemia were studied in 9 patients with coronary artery disease. In all patients typical anginal pain developed during pacing tachycardia, and in the postpacing beat, left ventricular end-diastolic pressure increased from 14 ± 4 to 26 ± 5 mm Hg (mean ± standard deviation, p < 0.01), relaxation time constant increased from 44 ± 9 to 59 ± 7 ms (p < 0.01) and ejection fraction diminished from 63.1 ± 9.1 to 52.8 ± 10.8% (p < 0.01). However, peak rate of early left ventricular filling obtained from frame-by-frame analysis of left ventriculograms did not change significantly. The time difference from segmental peak lengthening to left ventricular peak filling increased significantly in the ischemic segment (32 ± 30 vs 77 ± 49 ms, p < 0.05). Chamber stiffness constant of a viscoelastic model increased significantly from 0.0177 ±0.01 to 0.0354 ± 0.015 (p < 0.01) without change in chamber viscosity constant. In the ischemic segment, peak rate of lengthening decreased by 45% with ischemia, and peak rate of lengthening normalized for the end-diastolic segment length by 36%. However, peak rate of lengthening normalized for the extent of systolic shortening did not change. The control segment showed a tendency to increase in these 3 parameters, but the changes were not statistically significant. Thus, peak rate of segmental myocardial lengthening decreased with ischemia because of a decrease in segmental shortening. Peak rate of global left ventricular filling did not decrease with ischemia despite impairment in isovolumic relaxation, asynchrony in left ventricular filling, an increase in chamber stiffness and a decrease in the peak rate of segmental lengthening in the ischemic segment because of an increase in the peak rate of lengthening in the nonischemic segment secondary to an increase in left ventricular filling pressure.

Contractile function of heterogeneously perfused myocardium in conscious dogs.

The contractile function of heterogeneously perfused segments (HET) after circumflex coronary artery occlusion (CAO) was examined in conscious dogs. At 1 h after CAO, regional shortening (SH) in nonischemic segments did not change from pre-CAO base line, and regional endocardial blood flow (REBF) increased (P less than 0.05) to 1.52 +/- 0.20 from 1.06 +/- 0.08 ml.min-1.g of tissue-1. In ischemic segments, SH was replaced by paradoxical bulging, and REBF averaged 0.07 +/- 0.02 ml.min-1.g of tissue-1. In HET with one crystal of each pair in nonischemic myocardium and the other in severely ischemic myocardium, SH at 1 h after CAO was reduced (P less than 0.01) by 53.2 +/- 3.4%. REBF maps constructed with serial sections of ventricular rings containing the crystals revealed that in HET 50 +/- 5% of the myocardium was ischemic. Therefore, in the acute phase of ischemia, the reductions in SH in HET were proportional to the amount of ischemic myocardium between recording sites. In HET, SH significantly recovered (P less than 0.01) over 4 wk after CAO but remained depressed by 26.8 +/- 5.1%. In contrast, SH in ischemic segments did not improve after CAO. In HET, the effects of inotropic stimulation and changes in left ventricular afterload on SH (as percent of base line) were similar before and at 1-4 wk after CAO. Thus, in HET, the level of dysfunction is acutely determined by the amount of ischemic myocardium between recording sites. Over 4 wk after CAO, SH improved substantially in these segments, and contractile function was not adversely influenced by an inotropic stimulation or an increase in ventricular afterload.

Changes in isovolumic segment shortening following acute coronary occlusion: disproportionate effects of anterior versus posterior ischemia

We evaluated the changes in left ventricular pressure and isovolumic segment shortening in both the ischemic and nonischemic areas following acute coronary occlusion in 12 conscious dogs instrumented for the measurement of subendocardial segment lengths perfused by the left circumflex coronary artery and left anterior descending coronary artery, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the left circumflex coronary artery. In 6 dogs, another occluder was installed around the proximal left anterior descending coronary artery. Under the resting conditions, the isovolumic segment shortening in the areas supplied by the left anterior descending coronary artery and the left circumflex coronary artery were 2.1 ± 0.5% (SE) and −0.1 ± 0.5% ( P < 0.01; versus values in the area of the left anterior descending coronary artery), respectively. During a 1-min occlusion of the left circumflex coronary artery, the isovolumic shortening in the anterior segment increased to 3.8 ± 0.5% ( P < 0.001; versus values in the basal state), while the posterior segment produced isovolumic elongation (− 2.2 ± 0.5%, P < 0.001; versus values in the basal state). By contrast, during a 1-min occlusion of the left anterior descending coronary artery, the extent of isovolumic bulge in the anterior segment and the augmentation in the isovolumic shortening in the posterior segment was less prominent compared with the occlusion of the left circumflex coronary artery. It is concluded that there is a significant isovolumic ventricular asynchrony between different areas of the left ventricle and the effects of coronary occlusion on the isovolumic contractile characteristics of the ischemic and nonischemic segments are recognized in terms of inherent ventricular asynchrony and changes in tension development due to ischemia.

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.

Overestimation of infarct size by quantitative two-dimensional echocardiography: the role of tethering and of analytic procedures.

Analyses of regional left ventricular systolic wall motion or thickening overestimate infarct size. We used quantitative two-dimensional echocardiographic analysis of systolic thickening and contrast two-dimensional echocardiography to evaluate causes for that overestimation. The following possibilities were considered: "tethering," defined as dysfunction of contrast-enhancing myocardium adjacent to ischemic or contrast-negative regions, and the role of standard center of mass analysis algorithms, which may overestimate wall motion abnormalities because of the axis shift produced by simultaneous systolic expansion of the ischemic segment and systolic contraction of the nonischemic segment. In the short-axis view in 12 animals, the echo contrast defect (ECD) occupied 32 +/- 7% of the left ventricular circumference. Extent of dysfunction by the center of mass analysis was 39 +/- 5% of the left ventricular circumference and correlation with ECD size was .68 (SEE = 5.2%). Thus 8 +/- 6% of the circumference of the left ventricle was assessed to be dysfunctional yet enhanced with contrast. Tethering accounted for only half of this (4 +/- 4% of left ventricular circumference) and involved less than 1 cm on either side of the ECD. The remaining overestimation by the center of mass analysis correlated significantly (r = .89, p less than .01) with the amount of systolic expansion of the ECD. This expansion of the ECD (increase in angle subtended by the ECD of 11 +/- 8%) was produced by the systolic shift in the center of mass toward the dysfunctional segment from contraction of the opposite, nonischemic segment.(ABSTRACT TRUNCATED AT 250 WORDS)

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 effect of afterload on the cardiodepressor reflex response to coronary artery occlusion in dogs.

The acute hemodynamic responses to anterior and posterior wall ischemia were examined at different afterloads in 30 open-chest anaesthetized dogs. Regional and global left ventricular responses to acute ischemia were also measured before and following bilateral cervical vagotomy in 18 dogs. As the preocclusion afterload (mean aortic pressure) was progressively raised with intravenous methoxamine, a significant decrease in stroke volume occurred following circumflex artery occlusion, whereas no change in stroke volume occurred following occlusion of the left anterior descending artery. Bilateral cervical vagotomy completely inhibited the decrease in stroke volume during circumflex occlusion at high afterload. Vagotomy had no effect on the hemodynamic response to acute anterior wall ischemia. Reversible cold vagal block in paced hearts at high afterload unmasked compensatory inotropy in the nonischemic anterior myocardial segment during circumflex occlusion. Restoring vagal tone by rewarming attenuated the fractional shortening of the nonischemic segment. The results indicate that a relationship exists between myocardial wall tension and reflex cardioinhibition during acute posterior wall but not anterior wall ischemia in dogs.

Reversal of rest myocardial asynergy during exercise: A radionuclide scintigraphic study

While exercise-induced segmental left ventricular wall motion abnormalities are well described, the phenomenon of improvement in certain asynergic segments during exercise in some patients remains a curiosity. To assess this unexpected finding, results were analyzed in 85 patients with wall motion abnormalities at rest who underwent two view (45 degrees left anterior oblique and anterior) exercise radionuclide ventriculography and exercise thallium-201 myocardial perfusion imaging. Wall motion was scored with a 5 point system (from 3 [normal] to - 1 [dyskinesia]); normalization or increase of 2 or more points with exercise signified improvement. Forty-eight patients (56%) had no change or further deterioration of wall motion at peak exercise, 15 (18%) showed both improvement of wall motion and deterioration and 22 (26%) showed only improvement of wall motion. Wall motion improvement during exercise was found in 57 (20%) of 279 segments with asynergy at rest. Of these 57 segments improving with exercise, 45 (79%) showed mild and 12 (21%) showed severe asynergy at rest. Only seven segments (12%) were associated with pathologic Q waves. Thallium-201 perfusion was normal in 44 segments (77%) while only 6 segments (11%) had reversible and only 7 (12%) had nonreversible thallium-201 defects. 1) wall motion that is abnormal at rest can sometimes improve with exercise; 2) this phenomenon generally occurs in zones without a Q wave or nonreversible thallium-201 defect. Hence, segments with abnormal wall motion at rest that show improvement with exercise appear to represent viable nonischemic segments.

Characterization of segmental collateral blood flow in the small intestine.

Collateral blood flow and the pressures and resistances determining that flow were measured between two adjacent segments of canine jejunum following acute occlusion of the arterial branch perfusing one of the segments (the "recipient" segment). Collateral flow was approximately 55% of control flow in the recipient segment. This flow was provided by an equal increment in arterial flow to the nonischemic ("donor") segment, such that pressures, resistances, and flows in the donor segment were not affected. Virtually all of the total collateral flow was derived from precapillary channels and was therefore available to the capillary bed of the recipient segment. Collateral flow was adequate to maintain the recipient segment in a nonischemic state, as indicated by the absence of a reactive hyperemia following release of the arterial occlusion. Selective occlusions of intramural or extramural collateral channels indicate that about two-thirds of the total collateral flow is derived from the extramural (marginal) vessels, while the remainder is supplied by intramural collaterals. For the most part collateral flow between adjacent segments is determined simply by the pressure gradient between connecting collateral channels.

Hyperkinetic contraction of a nonischemic segment of ischemic left ventricle in anesthetized dogs.

Regional myocardial function during acute coronary artery occlusion was studied with ultrasonic dimension gauges in 20 open-chest anesthetized dogs. Two pairs of ultrasonic crystals were implanted in the left ventricular free wall near the epicardium in an ischemic segment and in a control nonischemic segment, and the segment length (SL) and maximum velocity of systolic shortening (max dL/dt) were measured. In six dogs, the wall thickness (WT) was measured simultaneously in the same regions with sonomicrometry. Left ventricular pressure (LVP), aortic pressure (AoP), and plasma norepinephrine concentration in the coronary sinus (NECS) were also measured. The heart rate was kept constant (180 beats/min) with atrial pacing. The left anterior descending coronary artery was occluded at its distal portion without propranolol in 12 dogs (group 1) and 30 min after propranolol in eight dogs (group 2). In the ischemic region, coronary artery occlusion resulted in an increase in end-diastolic SL (50% at 3 min after occlusion in group 1, P less than 0.005), and a decrease in max dL/dt in systole (36% at 5 min after occlusion in group 1, P less than 0.02). In the nonischemic region, end-diastolic SL did not change significantly, but an increase in max dL/dt (29% at 10 min after occlusion in group 1, P less than 0.005) was observed in systole. Under propranolol (group 2), the results were similar to those of group 1. There were no significant changes in LVP, AoP, AoP, and NECS during occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of medial lamellar architecture in the pathogenesis of aortic aneurysms

The human abdominal aorta is particularly susceptible to the formation of aneurysms with atrophic walls. This aortic segment normally has fewer medial lamellar units than would be expected for a mammalian aorta of comparable diameter as well as far fewer medial vasa vasorum than would be expected for an aortic wall of comparable thickness. To test the hypothesis that ischemia and/or loss of normal lamellar architecture are predisposing factors for aneurysm formation, we used the pig thoracic aorta, which is furnished with 75 medial layers and vasa supplying the outer two thirds. Vasal blood flow was surgically ablated, and crushing injury was used to reduce the number of intact lamellar units. Mural ischemia alone resulted in necrosis of cells in the medial zone furnished by vasa but did not lead to aneurysmal dilatation, and all the fibrous tissue layers persisted during the 2-month observation period. Mechanical injury resulted in aneurysms in both ischemic and nonischemic aortic segments, but only if fewer than 40 intact lamellae remained and the average tension per lamellar unit exceeded three times the normal value of 1316 ± 202 dynes/cm (4543 ± 1624 for ischemic and 4087 ± 871 for nonischemic segments; p < 0.01 for each). We conclude that a critical reduction in the number of intact lamellar units results in aneurysmal dilatation. Protracted medial ischemia due to intimal plaque formation in the avascular abdominal aorta may eventually reduce the number of intact lamellae and favor the development of aneurysms.

Failure of pindolol and metoprolol to reduce the size of non-reperfused infarcts in dogs using area at risk techniques.

Recent studies have shown that long term mortality after acute myocardial infarction is reduced by chronic beta-blocker therapy, however, the mechanism is not well understood. Our objective was to determine whether the selective beta blocker, metoprolol, or the nonselective intrinsic sympathomimetic activity (ISA)-blocker pindolol, reduce infarct size as a function of an area at risk (AR) in a permanent infarction model in dogs and which blocker is preferable in regards to myocardial function. Dogs were instrumented with ultrasonic crystals to measure regional function in nonischaemic and infarct margin segments. Left ventricular (LV) pressures, LV dP/dt and heart rate (HR) were monitored. Dogs were subjected to a 6 h LAD coronary artery occlusion and were randomised to a control (n = 9), pindolol (n = 10), and metoprolol (n = 9) group. At 30 and 90 min post occlusion saline, pindolol (3 micrograms X kg-1 and 12 micrograms X kg-1) or metoprolol (12 micrograms X kg-1 and 48 micrograms X kg-1) were given intravenously. The in vivo AR was determined by autoradiography, the in vitro AR by postmortem dye infusion and the area of necrosis by tetrazolium staining. Pindolol and metoprolol decreased LV dP/dt by 20% (P less than 0.05). Metoprolol also decreased HR by 20% (P less than 0.05) and shortening of nonischaemic segments by 12% (P less than 0.05) following the 1st and 2nd dose. Function in infarct margin segments was not changed in either group. Blood flow, measured by microspheres, was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of early systolic and early diastolic regional function during regional ischemia in a chronically instrumented canine model

Depressed left ventricular function during the early part (first third) of both systole and diastole in the resting state have been reported to be sensitive indicators of coronary artery disease in patients with normal global function at rest. To evaluate the possible mechanisms of these findings, 11 dogs were chronically instrumented with segmental function sonomicrometers in the left circumflex and left anterior descending coronary artery distribution, circumflex coronary flow probes and cuff occluders, aortic flow probes and ventricular pressure transducers. Percent segmental function during the first third of systole and diastole was measured in the control state and with graded circumflex artery flow reductions. Significant decreases in early systolic function with ischemia in the circumflex artery distribution were partially offset by compensatory augmented shortening in the left anterior descending artery distribution. With ischemia in the circumflex distribution, there was prolonged contraction into diastole manifested as impaired relaxation. Simultaneously, in the left anterior descending artery distribution, there was minimal compensatory enhanced relaxation. These results suggest that early systolic dysfunction in ischemic segments may be offset by enhanced function in nonischemic segments, rendering minimal, if any, change in global systolic function. Early diastolic dysfunction in ischemic segments exceeds compensatory changes in nonischemic areas by two-to-four-fold. Hence, early diastolic functional indexes may be more sensitive indicators of ischemia at rest than early systolic functional indexes.

First ultra-short-acting beta-adrenergic blocking agent: Its effect on size and segmental wall dynamics of reperfused myocardial infarcts in dogs

Beta-adrenergic blocking agents have an established role in the treatment of myocardial ischemia, but precipitation of cardiac failure or bronchospasm may restrict their use in some patients with acute myocardial infarction or in those undergoing coronary bypass surgery. ASL-8052 is a new cardioselective ultra-short-acting beta blocker which allows abolition of beta blockade within 16 minutes on termination of an intravenous infusion. An investigation was made of the effect of ASL-8052 on myocardial infarct size, regional myocardial wall function, and hemodynamic features during a 3-hour experimental occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion in dogs. Twenty-two dogs (10 control, 12 treated) were instrumented for the measurement of left ventricular (LV) pressure, the first derivative of left ventricular pressure (LV dP/dt), systolic and diastolic aortic pressure, and heart rate. Two pairs of ultrasonic crystals were inserted into a nonischemic segment and an ischemic marginal zone segment to obtain percent segment shortening. The area of necrosis was determined by tetrazolium staining and expressed as a percentage of the in vivo area at risk obtained by autoradiography. Dogs in the control group received saline solution; in treated dogs, a continuous infusion of ASL-8052 was begun 15 minutes after occlusion with a dose “titrated” to reduce the heart rate by approximately 20% (100 to 150 μg/kg/min). After 3 hours of reperfusion, the amount of myocardial tissue necrosis, as a function of the in vivo area at risk, was significantly lower in ASL-8052-treated (48 ± 7%) than in control (73 ± 6%) dogs (p < 0.025). Upon reperfusion, segment shortening decreased in control dogs from −3.3 ± 1.1% after 3 hours of occlusion to −6.3 ± 1.9% (p < 0.05) 2 hours after reperfusion (that is, systolic bulging increased). This functional deterioration upon reperfusion did not occur in treated dogs. During the occlusion period, infusion of ASL-8052 caused a decrease in heart rate of 22 ± 3% (p < 0.001) and in LV dP/dt by 22 ± 4% (p < 0.05). Upon reperfusion, control dogs had an increase in heart rate of 26 ± 1% (p < 0.05). In treated dogs, heart rate did not change. Hence, infarct size, reperfusion tachycardia, and myocardial wall asynergy were reduced in ASL-8052-treated dogs. A potential advantage of this agent is that its short duration of action would allow rapid reversal of beta blockade if adverse effects developed.

Myocardial function in areas of heterogeneous perfusion after coronary artery occlusion in conscious dogs.

Regional myocardial function and blood flow in endocardial layers were correlated in myocardial segments subtending severely ischemic and adjacent, normally perfused myocardium in conscious dogs 1--3 weeks after recovery from coronary artery occlusion. With coronary artery occlusion induced by a hydraulic occluder, endocardial blood flow (measured with radioactive microspheres) and function (determined with an ultrasonic dimension gauge) in homogeneously nonischemic segments increased slightly but not significantly. In homogeneously ischemic segments, blood flow and function decreased (p less than 0.01) by 96 +/- 1% and 98 +/- 4%, respectively. In segments subtending zones of unequal perfusion, endocardial blood flow increased nonsignificantly in the myocardium surrounding the nonischemic crystal, while decreasing by 93 +/- 2% (p less than 0.01) in myocardium surrounding the ischemic crystal. Surprisingly, these segments behaved like homogeneously ischemic segments, i.e., endocardial shortening decreased by 92 +/- 6% (p less than 0.01). Thus, the failure to detect shortening despite normal perfusion of the myocardium surrounding one of the transducers suggest a potential problem with interpretation of regional function measurements or an inability of the apparently nonischemic myocardium to contract.

Intracoronary streptokinase thrombolytic recanalization and subsequent surgical bypass of remaining atherosclerotic stenosis in acute myocardial infarction: Complementary combined approach effecting reduced infarct size, preventing reinfarction, and improving left ventricular function

In 48 patients with acute myocardial infarction (AMI) the acutely thrombus-occluded coronary artery was successfully recanalized nonsurgically via catheter with intracoronary streptokinase (SK) infusion after a mean occlusion time of 3.1 ± 1.6 hours. In all cases residual high-grade fixed atherosclerotic stenosis remained after percutaneous transluminal coronary recanalization (PTCR). Subsequent aortocoronary bypass surgery (ACBS) circumventing the stenotic coronary artery was performed during the acute stage of myocardial infarction (within 10 days of AMI onset) in 34 patients and electively (longer than 10 days after AMI onset) in 14 patients. No patient died from early PTCR or from ACBS intervention. There were two late post-ACBS arrhythmogenic deaths, two patients suffered nonfatal reinfarction post ACBS several months after hospital discharge, only two had occasional post-ACBS angina pectoris, and one patient had post-ACBS mild heart failure. The remaining 41 post-ACBS patients were completely asymptomatic throughout long-term follow-up evaluation. In the left ventricular (LV) segment supplied by the initially occluded coronary artery, which was recanalized early by means of SK therapy and subsequently grafted, wall motion improved significantly from the acute to the postoperative stage in patients who underwent early surgery (from 13.6% ± 1.9% to 40.3% ± 2.7%, p < 0.001) and in the electively operated group (from 18.0% ± 7.1% to 48.2% ± 6.3%, p < 0.001). Ischemic wall motion was improved irrespective of whether or not the bypass graft circumventing the residual stenosis of the infarct vessel remained patent. Wall motion of nonischemic segments remained essentially unchanged. In the patients who underwent surgery in the early stage, the closure rate of the bypass graft to the infarct-related vessel was 17%, and in the electively operated group no graft was found to be occluded. In conclusion, coronary artery recanalization, achieved by means of early SK-PTCR therapy with subsequent ACBS, can be performed safely in patients with AMI, and the result will be marked improvement in LV segmental wall motion and global function, diminished reinfarction rate, and reduced incidence of angina pectoris, all benefits that are consistently maintained during long-term evaluation.

Use of Thermography to Predict Intestinal Viability and Survival After Ischemic Injury: A Blind Experimental Study

Reactive hyperemia is a characteristic of viable ischemic tissue that has been revascularized. In 14 normal dogs, segments of bowel were made ischemic for periods of 2--8 hours. Thermograms and surface temperature measurements of exposed ischemic and nonischemic segments were obtained before and every 5 minutes for 30 minutes after revascularization. Thermograms demonstrated uniform reactive hyperemia throughout the segments ischemic for 2--3 hours; hyperemia with some nonuniform, patchy areas in segments ischemic for 3--7 hours; and no hyperemic response in segments ischemic for 8 hours. All five dogs demonstrating uniform hyperemia survived and the bowels were found to be histologically normal. Four of the six dogs showing hyperemia with some nonuniform areas survived, but all six showed areas of transmural damage with fibrosis and scarring histopathologically. The three dogs with no hyperemic response died of pathologically proved bowel infarction. Our results indicate that thermograms can document the degree and extent of reactive hyperemia. Thermograms, therefore, may be an important aid in assessing bowel viability during surgery.