Michael D. McKown

Regional myocardial volume alterations induced by brief repeated coronary occlusion in conscious dogs

The purpose of this study was to evaluate whether brief repeated coronary occlusions induce changes in regional myocardial geometry at rest. Five conscious dogs were instrumented for the measurement of subendocardial segment length and transmural wall thickness in the ischemic area, subendocardial segment length in the normally perfused area, coronary flow and left ventricular pressure. After recovery from surgery, 180 (mean) 2 min coronary occlusions were given over a period of 20 days. The heart rate at rest, left ventricular peak systolic and end-diastolic pressures and peak positive first derivative of left ventricular pressure (dP/dt) remained unchanged throughout the experiment. In the normal area, the end-diastolic segment length at rest did not change significantly. By contrast, in the ischemic area, at 14 days after the initiation of repeated coronary occlusion, the end-diastolic regional cross-sectional area (product of segment length and wall thickness) at rest had increased by 9.7% (p less than 0.05); thereafter it decreased to 6.5% (p less than 0.05) above the value at rest before repeated occlusion despite an additional 6 days of coronary occlusions. At 10 days after the interruption of repeated occlusion, this value had regressed to 4.3% (p = NS) above control. These findings suggest the occurrence of regional myocardial hypertrophy confined to the ischemic area in response to the periodic ischemic stimulus.

Coronary collateral regression in conscious dogs.

To study the effect of long-term coronary reperfusion on regression of newly developed collateral vessels, the authors reoccluded the coronary artery for ten minutes following one to fifteen weeks of reperfusion. They repeated one- or two-minute occlusions of the left circumflex coronary artery (LCCA) in 8 conscious dogs. After 401 ±202 (SD) minutes of total LCCA occlusion time (35 ± 19 days), the LCCA occlusion produced no sustained reduction in regional myocardial shortening and negligible reactive hyperemia. Upon reocclusion following a long-term reperfusion, the subendocardial segment shortening in the region at risk deteriorated markedly. At two minutes of occlusion, percent systolic shortening showed minimal values and thereafter gradually returned to the preocclusion resting levels within six to eight minutes of occlusion. In the presence of a resting heart rate similar to that at the time of functional recovery during the LCCA occlusion, long-term reperfusion did not modify the time course of regional functional response to the prolonged coronary occlusion. It is concluded that the newly developed collateral vessels still serve as significant blood-conveying conduits following a considerable period of reperfusion, and it requires approximately six to eight minutes to restore regional myocardial function in the collateral dependent zone following coronary reocclusion.

Electrocardiographic evaluation of collateral development in conscious dogs

In seven conscious dogs, endocardial ST-segment changes within the central ischemic area at 2 min after coronary occlusion were compared with the amount of reactive hyperemia and collateral blood flow. With the use of ultrasonic dimension gauges implanted in the subendocardium perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), endocardial electrocardiograms and regional myocardial dimensions were simultaneously measured. Collateral vessels were developed by repeated 2 min LCCA occlusions during three weeks. Blood flow debt repayment following the release of LCCA occlusion was measured using a Doppler flowmeter. The collateral blood flow from LCCA to the area supplied by the occluded LAD was measured as a stepwise reduction in LCCA flow upon the release of LAD occlusion. With the attenuation of myocardial ischemia due to the collateral development, endocardial ST-segment shift revealed earlier restoration compared with subendocardial function. In the presence of mild ischemia, the ST-segment was still elevated. Thus, endocardial ST-segment changes serve as an indirect functional index of collateral development as well as regional myocardial function and blood flow debt repayment.

Changes in coronary flow following repeated brief coronary occlusion in the conscious dog

SummaryStudies were conducted in 12 conscious, unsedated dogs instrumented for measurements of subendocardial segment length in the area perfused by the left circumflex coronary artery, blood flow velocity of this artery, and left ventricular pressure. An externally inflatable pneumatic occluder was placed to occlude the circumflex coronary artery for selected durations at selected intervals. Resting coronary blood flow velocity was measured before and after collateral development induced by repeated brief coronary occlusion. Under conditions of comparable myocardial oxygen consumption, shown by the similar pressure-rate product, preocclusion resting coronary blood flow velocity of the repeatedly occluded artery decreased by 21.3% (P<0.001) in association with collateral growth. These findings strongly suggest that the perfusion territory of the collateralized artery decreases considerably secondary to the periodic ischemic stimulus.

Effects of dipyridamole on collateral flow and regional myocardial function in conscious dogs with newly developed collaterals.

SummaryStudies were conducted on six conscious dogs instrumented for measurement of subendocardial segment lengths in the area perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. Externally inflatable occluders were placed around the proximal LAD and LCCA. Collateral channels sufficient for the resting metabolic demands in the occluded LCCA perfusion territory were induced by repeated, brief LCCA occlusions. Dogs were then subjected to two consecutive brief periods of LAD occlusion. Dipyridamole (0.25 mg/kg) was injected intravenously 3 min prior to the second LAD occlusion. The collateral blood flow from the LCCA to the occluded LAD area was measured as the stepwise decrease in LCCA flow upon release of the LAD occlusion. During LAD occlusion after dipyridamole treatment collateral blood flow velocity decreased to 3.8±1.1 cm/s (±standard error) compared with a value of 4.9±0.9 cm/s measured during LAD occlusion without dipyridamole treatment. Percentage systolic segment shortening in the collateral dependent zone significantly deteriorated from 14.3±5.2 to 9.7±5.0% (p<0.05). Electrocardiograms taken simultaneously from endocardial ultrasonic transducers in the ischemic segment revealed significant increases in ST-segment level from 4.2±0.6 to 5.4±0.6 mV. These findings indicate that dipyridamolc adverscly affects the extent of myocardial ischemia in the collateral-dependent zone.

A modification of the Harper-McGinty microdrive for use in chronically prepared rabbits

We describe a modification of the Harper-McGinty microdrive for use with extracellular, microwire recording in conscious, chronically prepared rabbits. Improvements over existing designs are in ease of assembly and mechanical stability. The microdrive is easily fabricated with hand tools and readily available parts. In addition, assembly of the microdrive utilizes epoxy, avoiding the difficult task of soldering stainless steel parts. Finally, the microdrive is mounted directly to the skull enhancing mechanical stability and eliminating the need to allow space for screw travel. Importantly, this microdrive has proven to be durable as well as functional in our preparation.

Opening of Coronary Collaterals by Repeated Brief Coronary Occlusions in Conscious Dogs

The collateral blood flow and regional myocardial function during a one- minute coronary occlusion were compared before and after multiple one-minute coronary occlusions. After repeated coronary occlusions, the collateral blood flow velocity increased significantly from 0.7 ± 0.1 (SE) to 2.0 ± 0.2 cm/sec (p < 0.05), and the blood flow debt repayment decreased from 326±26% to 189 ± 12 % (p < 0.05). The systolic segment shortening in the collateral depend ent zone improved slightly. Thus, the native coronary collateral vessels open in response to a repeated ischemic stimulus.

Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs.

The purpose of the present study was to compare the effects of nitroglycerin and diltiazem on coronary collateral circulation. Studies were conducted in 8 conscious dogs instrumented for the measurement of left circumflex coronary artery (LCCA) flow, subendocardial segment lengths in areas perfused by the LCCA, and left anterior descending coronary artery (LAD). Brief, repeated LCCA occlusions sufficiently developed collateral vessels for the resting metabolic requirement in the LCCA region. One week following the cessation of repeated LCCA occlusions, two-minute coronary occlusions with and without drug pretreatment were performed on separate days. The ischemic responses to coronary occlusions were not altered by diltiazem (50 μg/kg, IV), but nitroglycerin (5 μg/kg, IV) attenuated myocardial ischemia definitely. The authors conclude that nitroglycerin produces greater effects than diltiazem in attenuating myocardial ischemia in the collateral dependent zone when effects of each drug on systemic and coronary circulation were minimized by pretreatment with small doses.

Changes in regional myocardial cross-sectional area during brief coronary occlusion and reperfusion in conscious dogs☆

The effect of a brief period of coronary occlusion on a regional myocardial cross-sectional area was studied in 6 conscious dogs. Subendocardial segment length and wall thickness were continuously measured with a sonomicrometer in the central ischemic area perfused by the left circumflex coronary artery during a 2-min circumflex occlusion and subsequent reperfusion. Measurements were repeated before and after collateral development induced by 180 +/- 30 (SEM) 2-min circumflex occlusions (20 +/- 3 days). In order to evaluate the changes in regional myocardial volume, end-diastolic regional cross-sectional area was calculated as a product of end-diastolic segment length and wall thickness. Before collateral development, end-diastolic regional cross-sectional area transiently decreased 1.4 +/- 0.6% (NS) at 10 sec following sudden coronary occlusion, thereafter gradually increased to 3.7 +/- 1.0% (P less than 0.05) at the end of a 2-min occlusion. At 10 sec of reperfusion, end-diastolic regional cross-sectional area further increased to 7.0 +/- 1.1% (P less than 0.05) probably due to increased intravascular volume. Increase in end-diastolic regional cross-sectional area was still 2.5 +/- 0.6% (NS) at 3 min after the release of occlusion. After collateral development, the changes in end-diastolic regional cross-sectional area were 0.1 +/- 0.1% (NS), 0.4 +/- 0.3% (NS), 1.0 +/- 0.6% (NS) and 0.2 +/- 0.4% (NS), respectively. Thus, a significant increase in the regional myocardial cross-sectional area occurs during a brief period of coronary occlusion and reperfusion.

A Conscious Animal Model for Studies of Coronary Collateral Blood Flow Dynamics

We describe a new animal model and protocols for measurements of the rate of development of coronary collateral perfusion stimulated by repetitive episodes of regional, reversible myocardial ischemia in conscious dogs and for measurements of the integrated effects of interventions on collateral perfusion after development of collaterals. Examples of the results are illustrated and potential sources of errors are identified. We propose this model to complement the other in vitro and in vivo models for studies of coronary collateral dynamics in conscious animals.