The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

SUMMARY Measurements of cerebral spinal fluid pressure, arterial pressure, and internal carotid artery blood flow were obtained in a series of patients during a Valsalva maneuver. During straining (phase II), an 11% reduction in mean arterial pressure was associated with a 21 % decrease in internal carotid flow from control values; and following release (phase IV), the 19% increase in mean arterial pressure produced a 22% increase in internal carotid artery flow. Perfusion pressure computed as the mean arterial pressure minus cerebral spinal fluid pressure and internal carotid artery blood flow were used to calculate an index of cerebral vascular resistance. The data indicate that a modest but significant decrease in vascular resistance occurred during phases II and III followed by return to control levels during phase IV. These changes in vascular resistance were not rapid enough or of sufficient magnitude to maintain constant cerebral perfusion during the Valsalva maneuver. Stroke Vol 15, No I, 1984 THE PRECISION with which cerebral vascular blood flow can be maintained at a constant value during rapid changes in perfusion pressure has not been defined in man primarily due to the methodologic limitations encountered in measuring phasic cerebral blood flow. Quantitative measurements of phasic internal carotid artery flow have been obtained in man with an electromagnetic flowmeter and can be used as an index of cerebral flow.2 -3 The Valsalva maneuver is associated with marked changes in arterial pressure and thus, can be used to study the effects of rapid changes in arterial pressure on cerebral blood flow. 9 The purpose of this study was to measure the internal carotid artery blood flow and to compute for the first time the changes in cerebral vascular resistance which occur accompanying a brief Valsalva maneuver in a series of nine patients. MethodsNine male patients were studied who had been hospitalized on the Neurosurgical Section of the Veterans Administration Hospital, Durham, North Carolina. In each patient subtotal resection of a supratentorial malignant brain tumor had been carried out from 10 to 20 days previously. The data described in this report were obtained during exposure of the carotid vessels so that an antitumor agent (S-l 12, a chlorethylthioacetamide, Sfxg/kg) could be infused directly into the internal carotid artery. This drug was given immediately after the completion of the studies described. The informed consent of each patient was obtained.* At the time of study, the patients were alert and showed no major neurological deficits. The cerebrospinal fluid (CSF) pressure was less than 250 mm H 2 O. *This investigation was carried out under the procedures currently applicable for human investigation. Before the surgical procedure the patients were premedicated with 50 mg of meperidine and 25 mg of promethazine. Local anesthesia was accomplished with injections of lidocaine. The common carotid artery and proximal portions of both the internal and external carotid arteries were exposed, ...

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Ten normal and four transplanted canine jugular vein segments and four human saphenous vein segments were studied to determine the in vitro static elastic properties of venous tissue and their modification by transplantation into the arterial system. Both the intraluminal pressure and the longitudinal force were varied, and the resulting dimensions were recorded photographically. Venous segments manifested a hysteresis response but showed minimum tendency to creep. The pressure-strain relationships were curvilinear with an initial, highly compliant phase over the physiological venous pressure range followed by a relatively noncompliant phase. This transition occurred at lower pressures for jugular segments than it did for saphenous segments. In contrast, comparable-sized canine carotide artery segments did not show this essentially noncompliant phase over the pressure range studied (0 to 200 cm H2O). At comparable pressures and strains, the jugular vein segments were stiffer than the saphenous vein segments in both the circumferential and the longitudinal directions. At comparable strains, the saphenous vein moduli were similar to those in the carotid artery segments. Jugular segments transplanted into arterial circuits became virtually noncompliant and markedly inhomogeneous, with wall thickening and a histologic picture of intimal proliferation. They showed no tendency to "arterialize," that is, they failed to assume either the elastic or the histologic characteristics of arterial tissue.

SUMMARY This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7-10 pm in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 ± 0.03 (SE), 0.39 ± 0.05, 0.39 ± 0.04, and 0.53 ± 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmural layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.UNDER BASAL conditions the myocardium extracts nearmaximum amounts of oxygen from the arterial blood.