LAD Region Research Articles

Improved myocardial protection by antegrade perfusion in combination with coronary sinus occlusion in the presence of left anterior descending artery obstruction.

The present study was undertaken to evaluate the improved protection of antegrade aortic root perfusion combined with intermittent coronary sinus occlusion (APCSO) for the 1-hour ischemic myocardium in the presence of left anterior descending artery occlusion, 12 dogs were divided into 2 groups: anteperfusion (AP) alone (n = 6) and APCSO (n = 6). The experimental results showed that APCSO provided a better cardioplegic distribution and a lower hypothermia (15.6 degrees C versus 17.2 degrees C) in the occluded LAD region, compared with AP. After ischemia, cardiac index and left ventricular stroke index recovered excellently in APCSO (128% to 141% and 115% to 158% of preischemic values, respectively), and much worse in AP (69% to 82% and 53% to 73% of preischemic values, respectively). Our study has confirmed that APCSO is superior to AP in myocardial protection in the presence of coronary artery occlusion.

Postischemic recovery of mitochondrial adenine nucleotides in the heart.

Adenine nucleotides (AdNs) are lost from the mitochondrial fraction of the heart cell during ischemia. It is unknown whether this pool of AdNs can be replenished after reperfusion. The purpose of this study was to evaluate the postischemic recovery of the mitochondrial AdN pool. The left anterior descending coronary artery (LAD) of the canine heart was occluded for 30 minutes followed by either no reflow, 30-minute reflow, 1-day reflow, or 7-day reflow. Systolic shortening in the LAD-supplied region was absent during occlusion but recovered to approximately 30% of preocclusion values during early reperfusion. Mitochondrial and tissue AdNs (ATP, ADP, and AMP) were determined in the LAD-supplied and left circumflex-supplied (control) regions of the heart. The AdN content (expressed as percent of control values) of mitochondria from the LAD region was 55 +/- 10% (p less than 0.002), 64 +/- 7% (p less than 0.001), 81 +/- 6% (p less than 0.03), and 94 +/- 8% for the no-reflow, 30-minute-reflow, 1-day-reflow, and 7-day-reflow groups, respectively. The AdN content (expressed as percent of control values) of tissue samples from the LAD region was 52 +/- 9% (p less than 0.002), 48 +/- 12% (p less than 0.02), 68 +/- 5% (p less than 0.002), and 70 +/- 9% for the no-reflow, 30-minute-reflow, 1-day-reflow, and 7-day-reflow groups, respectively. There was a good correlation between mitochondrial and tissue AdN (r = 0.95). Using initial exchange rates, adenine nucleotide translocase activities of mitochondria from the LAD and control regions were not significantly different. State 3 respiration of LAD mitochondria was depressed (approximately 25%, p less than 0.05) only in the no-reflow group. Acceptor control ratios of the LAD mitochondria were not significantly different from control values in any group. After 30 minutes of regional ischemia, postischemic restoration of the mitochondrial AdN pool occurs between 1 and 7 days; this restoration is preceded by recovery of respiratory and adenine nucleotide translocase functions. Although the abnormally low levels of AdN persist in the mitochondrial compartment during the early reperfusion period, postischemic contractile dysfunction cannot be explained by depressed mitochondrial respiratory activity.

Mechanism of global functional recovery despite sustained postischemic regional stunning.

The mechanisms whereby reperfusion of a 20-minute coronary occlusion result in global functional recovery despite persistent regional dysfunction were studied in 11 open-chest reflex-blocked dogs. Pressure-volume and pressure-thickness relations were simultaneously determined before, during, and after reperfusion of left anterior descending artery (LAD) occlusion. Wall thickness was determined by sonomicrometry in both ischemic and remote regions. Chamber systolic function was assessed by end-systolic pressure-volume relations (ESPVR) obtained by conductance catheter and defined by a slope (Ees) and volume shift at a common end-systolic pressure (delta Ves). LAD occlusion produced regional systolic thinning (-7 +/- 6%) and global left ventricular dysfunction (ESPVR shifted rightward (delta Ves = +8.6 +/- 5.1 ml, p less than 0.001) with no Ees change). After nearly 1 hour of reperfusion, LAD region thickening remained markedly reduced at 4 +/- 7% (versus 23 +/- 8%, control), yet chamber systolic function fully recovered (ESPVR shifted back leftward delta Ves = -8.9 +/- 6.5 ml). Ischemia induced a leftward shift and systolic thinning of LAD region pressure-thickness relations. Reperfusion returned end-systolic pressure-thickness relations halfway to their control position and diastolic relations fully to control position. This was primarily due to increased passive stiffening in about half the hearts and a partial return of active function in the remaining ones. The net effect was to eliminate systolic thinning over a physiological loading range, thus normalizing chamber systolic performance. Reflex activation, remote hyperfunction, or altered chamber loading did not account for the postreperfusion disparity between global and regional function. These data suggest a mechanism to account for greater functional benefits of reperfusion beyond that anticipated from regional wall motion analysis.

Nitrous oxide does not worsen myocardial ischaemia following beta-receptor blockade in isoflurane anaesthetized dogs

The effect of nitrous oxide (N2O) on ischaemic myocardium was investigated in the presence of beta-receptor blockade. Three anaesthetics were compared in each of six dogs: isoflurane 1.8% alone, isoflurane 1.4% with 50% N2O, and isoflurane 1.8% with 50% N2O. Heart rate (HR), systolic aortic blood pressure (SBP), and left atrial pressure (LAP) were held constant during the three treatments. The left anterior descending coronary artery (LAD) was cannulated and perfused with an autoperfusion circuit. Systolic segment length was measured with a sonomicrometer in the LAD and circumflex regions. Regional myocardial blood flow was measured using radioactive microspheres. Propranolol was administered intravenously and then measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 30%. The substitution of 50% N2O for 0.4% isoflurane had no effect on systolic shortening or transmural myocardial blood flow in the ischaemic or normal region. When N2O was added to 1.8% isoflurane, systolic shortening decreased by 34.6% in the ischaemic and 57.3% in the normally perfused region, while transmural myocardial blood flow distribution did not change significantly. The decrease in shortening was therefore not due to increased ischaemia. These results were similar to those of a previous experiment which was identical except that beta-blockade was absent. It is concluded that beta-receptor blockade does not markedly alter the response of normal or ischaemic myocardium to N2O.

Direct CO2 laser “revascularization” of the myocardium

Evidence of regional myocardial perfusion and contractile function after direct CO2 laser myocardial revascularization (DLR) is lacking. We examined myocardial segment shortening, adenine nucleotide concentrations, and regional blood flow after DLR of the left anterior descending coronary artery (LAD) distribution before and after its proximal ligation in seven anesthetized conditioned dogs. Sonomicrometry assessed myocardial fiber shortening and radioactive microspheres were used to estimate baseline regional blood flows. Cardiopulmonary bypass was followed by cardioplegia arrest. Laser channels (1 mm diameter) were made every 3 to 5 mm in the LAD region with an 80 watt Laser-sonics CO2 unit. Bypass was terminated, the LAD occluded, and parameters reassessed. Core samples of myocardium from the lased LAD and control circumflex area were taken to assess adenine nucleotides. After occlusion, LAD distribution blood flow and myocardial shortening were reduced to pre-lasting ischemic controls. Adenine nucleotides were reduced in the LAD region relative to the control CMX area. DLR cannot be relied upon to acutely revascularize the ischemic myocardium.

Effect of Halothane and Isoflurane on Postischemic “Stunned” Myocardium in the Dog

Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic "stunned" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area.(ABSTRACT TRUNCATED AT 250 WORDS)

Programmed electrical stimulation after myocardial infarction and reperfusion in conscious dogs

The hemodynamic and electrophysiologic variables and the inducibility of arrhythmias were studied before coronary artery occlusion (CAO, 4h) and on days 4, 14, and 28 of the late reperfusion phase in conscious, chronically instrumented dogs. Despite a lack of significant changes in the hemodynamic and the electrophysiologic variables, the response to programmed electrical stimulation (PES) before and after CAO with subsequent reperfusion varied substantially. Before intervention arrhythmias such as sustained ventricular tachycardia (SVT) or ventricular fibrillation (VFib) could not be induced by PES via ultrasonic crystals located subendocardially (LAD and LCX region) or via common stimulation electrodes (right ventricle) in any of six instrumented animals. All six animals were inducible after CAO and reperfusion. Five animals showed SVT and one animal showed VFib in response to stimulation on days 4 and 14 of the late reperfusion phase after CAO. On day 28 four animals showed SVT, and two showed VFib. Antiarrhythmic drug testing carried out in the late reperfusion phase with lidocaine (1 mg/kg bolus followed by continuous infusion) revealed 50% efficacy at a dosage of 40 μg/kg/min, 100% at 80 μg/kg/min, and 67% at 120 μ/kg/min. The persistent inducibility of arrhythmias for the entire experimental period of 24 days may be attributable to the following features of our model: 1. 1. Electrical stimulation carried out from three different locations. 2. 2. The use of up to three extrastimuli in the PES studies. 3. 3. The use of conscious dogs during CAO, reperfusion, and PES. This novel experimental approach thus promises to be of clinical relevance for the investigation of new antiarrhythmic drugs.

Regional myocardial metabolism and electrolyte balance during acute ischemia in dogs

The relationships among regional (ischemic and non-ischemic) myocardial extracellular (coronary venous) potassium concentration, potassium-sodium concentration ratio, acid-base balance, and metabolism of glucose and lactate were evaluated in 14 anesthetized dogs in which ischemia was produced by transitory left anterior descending coronary artery (LAD) occlusion. Coronary blood samples were obtained from the specific regions by using coronary arterial and venous catheters placed directly into the vessel supplying (or draining) that region. During ischemia, in coronary venous blood sampled from the ischemic area, pH decreased, and PCO2, base deficit, potassium concentration, and the potassium-sodium ratio increased. In LAD venous blood samples obtained during LAD occlusion, the percentage change in potassium concentration was inversely related to the percentage change in PCO 2 ( r = −0.634, P < 0.05), but not to the percentage change in hydrogen ion concentration ( r = −0.339, P > 0.05). During ischemia, arteriovenous O 2 content difference in the LAD region increased from 8.54 ± 0.73 vol % to 10.71 ± 0.73 vol %; lactate extraction became negative (indicating net production), values decreasing from 27.76 ± 4.49% to −138.10 ± 16.81 % ( P < 0.05); and glucose extraction increased from 14.57 ± 2.88% to 19.01 ± 6.06% (0.05 < P < 0.1). These observations indicate that efflux of potassium from the myocardium during ischemia is linked to tissue hypoxia, increased glucose extraction, lactate production, and extracellular acidosis. A further contributor to potassium release, failure of the normal membrane-bound, energy-requiring ion pump, cannot be excluded by these data. With the model used in this study, blood can be sampled from discrete regions of the heart, which enables the study of interactions between pharmacologic agents, such as anesthetics, and the metabolic abnormalities produced by acute ischemia.

Effect of complement depletion on O2 supply and consumption in ischemic dog myocardium.

The purpose of this study was to determine whether depletion of serum complement can decrease the severity of an ischemic episode by improving regional O2 supply and consumption parameters in the ischemic region of the heart. Fourteen anesthetized dogs with serum complement intact or depleted (100 U/kg cobra venom factor given 8 hrs before) were subjected to left anterior descending coronary artery (LAD) occlusion for 6 hrs. Myocardial blood flows were determined before and 6 hrs after LAD occlusion using radioactive microspheres. Regional arterial and venous O2 saturations were determined using microspectrophotometry. In control animals, flow decreased from 122 +/- 42 to 13 +/- 14 ml/min/100 g (mean +/- SD) in the occluded LAD region. With complement depletion, LAD occlusion resulted in a flow reduction in the ischemic region (38 +/- 29 ml/min/100 g), but to a lesser degree than seen in the same region in control animals, especially in the subendocardium. O2 consumption was decreased in the ischemic region of both treatment groups, though O2 consumption was higher in this region in complement depleted animals compared to the values in control animals. The O2 supply/consumption ratio was decreased similarly in the ischemic region of control and complement depleted groups. Thus, with complement depletion, flow to the ischemic zone was improved but this region was still flow restricted. The flow increase during complement depletion was sufficient to allow an increased O2 utilization in the ischemic region.

Naloxone enhances myocardial responses to isoproterenol in dog isolated heart-lung.

Intracoronary injection of naloxone produces rapid local increases in myocardial performance. The role of beta-adrenergic activation in this response was investigated. Naloxone was injected into the left anterior descending artery (LAD) of anesthetized dogs with the adjacent circumflex territory serving as control. Naloxone increased the contractile state locally in the LAD region. Pretreatment with propranolol eliminated the regional inotropic response. An isolated heart-lung model was set up, and isoproterenol dose responses were determined. When repeated after naloxone, contractile (dP/dt) responses to isoproterenol were both augmented and prolonged. In a third study imipramine was used to determine whether naloxone might act by reducing neuronal uptake of the isoproterenol. Imipramine extended the effect of isoproterenol temporally but did not alter the peak response. Adding naloxone increased the peak response to isoproterenol and maintained it above the extended imipramine response. The data support the concept that the blockade of opiate receptors facilitates adrenergic activity mediated by myocardial beta 1-receptors 1) directly through postsynaptic mechanisms, 2) indirectly through beta 2-mediated release of norepinephrine, or 3) via interference with nonneuronal disposal mechanisms.

The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration.

When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid (123I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated on validity. This was done by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients undergoing cardiac catheterization were studied. Scintigraphy was performed after the injection of 123I-HDA into the left coronary artery and after i.v. injection. Half-time values were calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123I-HDA is incomplete, as it resulted in half-time values that were higher than those of the i.c. study.

Ventricular arrhythmias and regional blood flow in acute and subacute myocardial infarction: effects of the carboxylic ionophore monensin.

Summary: The effects of monensin (75 μg/kg, i.v.) on regional myocardial blood flow and ventricular arrhythmias were studied in 15 anesthetized dogs following ligation of the left anterior descending coronary artery (LAD). During the acute stages of ischemia (n = 7), atrial pacing at a constant rate (224 ± 8 min 1) resulted in fractionation and delay of potentials recorded from the epicardial surface of the ischemic zone which preceded the onset of ventricular tachycardia (VT). The progression of ischemic zone conduction delay and the time to appearance of ventricular arrhythmias were reproducible with repeated occlusions (173 ± 13 see). Blood flow in the subepicardium of the LAD region decreased following occlusion (174 ± 27 to 13 ± 3 ml/min/100 g). and was not significantly affected by monensin (75 μg/kg.i.v). although blood flow in the normal zone increased markedly (156 ± 16 to 519 ± 70 ml/min/100 g). In this series of experiments. monensin accelerated the progression of conduction delay in the ischemic zone and decreased the time to onset of VT (138 ± 12 sec, p

The effects of nitroglycerin on coronary collaterals and myocardial contractility.

Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2(1/2)-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 mug) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is ischemic, collaterals are unresponsive to TNG, suggesting that these collaterals dilate fully when the regions from which they originate become ischemic.