Experimental and Clinical Studies on the Effect of Intra-Aortic Balloon Pumping for Cardiogenic Shock Following Acute Myocardial Infarction

The effect of intra-aortic balloon pumping (IABP) on cardiogenic shock following acute myocardial infarction was studied experimentally and clinically. Effects of IABP on hemodynamic and electro-cardiographic changes were studied with cardiogenic shock which was produced by multiple ligation of the coronary artery in dogs. Consequently, the hemodynamics as well as the ECG could be improved by diastolic augmentation and systolic unloading during IABP. But, these favorable effects of IABP were not seen in dogs whose infarcted area involved more than 50% of the free wall of the left ventricle. These facts were seen clinically in three autopsied cases. IABP was also attempted in dogs with complications such as ventricular septal defect (VSD) and mitral regurgitation (MR) following acute myocardial infarction, and significant improvement was obtained by IABP. No effects of IABP were seen in these series, however, when the value of the pulmonary-to-systemic flow ratio was over 4.5 in the VSD group and the mean left atrial pressure was more than 30 mmHg in the MR group. Clinically, IABP was employed in 16 patients with cardiogenic shock secondary to acute myocardial infarction. Six (37.5%) were weaned from IABP. It can be concluded that IABP is effective in improving hernodynamics as well as the ECG.     

Effect of Pulsatile and Nonpulsatile Assist on Heart and Kidney Microcirculation with Cardiogenic Shock

Abstract: To estimate microcirculation of the heart and kidney in pulsatile and nonpulsatile-assisted circulation, a comparison study was done using a swine model. Acute myocardial infarction was made by ligation of the left coronary artery branches. After cardiogenic shock, animals were divided into 3 groups as follows: Group C (n = 6), no assist provided; Group NP (n = 6), assisted by a nonpulsatile pump (Bio-Medicus BP-80); Group P (n = 6), supported by a pulsatile pump (Nippon Zeon). Left coronary artery flow, endocardial and epicardial regional flows, and renal cortex and medulla tissue blood flows were measured. Left coronary artery flow and endocardial and epicardial tissue blood flows decreased in cardiogenic shock, and they recovered to the control level soon after support in both Group N and Group P. Renal medulla and cortex tissue blood flows decreased in cardiogenic shock, and these flows did not recover in either Group N or P. However, cortex blood flow in Group P did improve, but it did not improve in Group N. These results suggested that pulsatile assist was more effective than nonpulsatile assist for microcirculation after cardiogenic shock to avoid deterioration of major organ functions.     

Evaluation of Regional Myocardial Nutrient Perfusion Following Selective Retrograde Arterialization of the Coronary Vein

The effects of selective coronary vein occlusion (SCVO) and selective retrograde arterialization of the coronary vein (SRACV) on nutritional myocardial blood flow was evaluated in 10 dogs with radioactive microspheres. SRACV was performed with a shunt interposed between the aorta and the great cardiac vein (GCV). Following ligation of the GCV, measurements were performed before and after ligation of the middle portion of the left anterior descending coronary artery (LAD) and then after 15 and 30 minutes of SRACV. The myocardium was divided into three regions: circumflex coronary artery (served as control), high LAD (proximal to arterial occlusion; supplied by both SRACV and coronary flow), and low LAD (distal to arterial occlusion; supplied by SRACV alone).SCVO decreased mean myocardial blood flow with increased distribution to the endocardium. SRACV to normally perfused myocardium did not significantly change myocardial blood flow; however, SRACV to acutely ischemic myocardium restored less than 50% of the decrease in myocardial blood flow. SRACV does not appear to greatly enhance blood flow to ischemic areas of the myocardium and may significantly reduce flow on the basis of venous occlusion alone.     

Intraaortic balloon counterpulsation: its influence alone and combined with various pharmacological agents on regional myocardial blood flow during experimental acute coronary occlusion

We investigated the separate and combined effects of pharmacological and intraaortic balloon pump (IABP) support on regional myocardial blood flow in an experimental model of acute myocardial ischemia. Chloralose-anesthetized dogs were ventilated with an oxygen-air mixture, and cardiac output, arterial pressure, and heart rate were held constant. Treatment was begun 20 minutes following permanent ligation of the left anterior descending coronary artery (LAD). We evaluated the following pharmacological interventions: 25% hypertonic mannitol, isosorbide dinitrate, methyl-prednisolone sodium succinate, and propranolol. We measured left ventricular hemodynamics and intramyocardial blood flow by the radioactive microsphere technique prior to treatment and at 15-minute intervals thereafter. Compared with control measurements 20 minutes following LAD ligation, collateral blood flow to ischemic myocardium tended to decrease with no treatment. Treatments with the four pharmacological interventions and with IABP alone produced no significant improvement in collateral blood flow to ischemic myocardium 15 minutes following treatment. In contrast, mannitol, isosorbide dinitrate, and propranolol, each combined with IABP support, produced significant improvements in collateral flow within the same time periods. In nonischemic myocardium, combined pharmacological and IABP treatment did not enhance myocardial blood flow above that obtained with the pharmacological agents alone. The most effective combination of mechanisms for improving the ischemic region's myocardial blood flow appeared to be a reduction of extravascular coronary flow resistance coupled with a simultaneous increase in diastolic arterial pressure.     

Combined effects of paired ventricular pacing and propranolol on ischemic myocardial injury.

In 30 dogs, acute myocardial infarction was produced by coronary artery ligation, and the dogs were divided into three groups. Group A animals (n = 10) had coronary ligation only. In Group B (n = 12), paired ventricular pacing was initiated 30 minutes following infarction. Group C (n = 8) was identical to Group B except that propranolol, 0.2 mg per kilogram of body weight, was given intravenously 10 minutes before the initiation of paired ventricular pacing. High-fidelity left ventricular pressures, acceleration of aortic flow (max dQ/dt), coronary sinus creatine phosphokinase (CPK), and epicardial mapping were recorded serially before and after coronary artery ligation. The incidence of ventricular fibrillation was not statistically different in Groups A and C (2/10 and 2/8, respectively), but it was higher in Group B (6/12) (p < 0.05). The maximum first derivative of left ventricular pressure divided by isovolumic-developed pressure [(dP/ dt)/P] and max dQ/dt during the 30 minutes following ligation were similar in all groups; however, in Group B, max (dP/dt)/P and max dQ/dt increased after the initiation of paired ventricular pacing (p < 0.01) while in Group C the same factors increased insignificantly. Coronary sinus CPK as well as the sum of ST segment elevations and the number of sites showing ST segment elevation increased significantly more in Group B and significantly less in Group C compared with control Group A. This study suggests that in experimental acute myocardial infarction, the combined effects of paired ventricular pacing and propranolol decrease myocardial ischemic injury without altering left ventricular performance or increasing the incidence of ventricular fibrillation.     

Acute myocardial infarction due to left main coronary artery occlusion

OBJECTIVE: Acute myocardial infarction due to left main coronary artery occlusion remains catastrophic and mostly fatal due to severe cardiogenic shock and arrhythmia. METHODS: We studied 13 patients undergoing coronary artery bypass grafting for acute myocardial infarction due to left main coronary artery occlusion to clarify the optimal management of these difficult patients. RESULTS: In-hospital mortality was 46.2% (6/13). Revascularization was achieved by catheter intervention followed by bypass surgery in 7, and bypass surgery alone in 6. Two bypass surgery patients without catheter intervention had collateral flow to the left coronary artery, with the right coronary artery dominant. The time from onset to recanalization in the survival group was significantly shorter than in the early death group. CONCLUSIONS: Emergency intervention to preserve left ventricular function or right coronary artery dominant and collateral blood flow to left coronary arteries is important for improving the prognosis of patients with acute myocardial infarction due to left main coronary artery occlusion. If residual left main coronary artery stenosis is significant or other proximal coronary stenosis exists after catheter intervention, early coronary bypass surgery may improve long-term survival.     

Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.     

Effect of RVAD for right heart failure involved with right ventricular infarction--especially studies of myocardial regional blood flow and epicardial mapping electrocardiography

In recent years, the number of cases in which a ventricular assist device is required for serious heart failure not responding to conventional mechanical circulatory assistance, has been increasing. It should be pointed out, however, that the majority of the new device is to assist the left ventricle, and that the effect of right ventricular assist device (RVAD) has not been fully clarified yet. The effect of RVAD and intra-aortic balloon pumping (IABP) on right ventricular failure due to right ventricular infarction was studied in swine. Right ventricular infarction was made by means of right coronary artery ligation. After preparation of right ventricular infarction, both mean aortic pressure and cardiac output were reduced and elevated central venous pressure, increased right ventricular end-diastolic pressure, dilatation of right ventricular free wall, were noted and diagnosed as a cardiogenic shock due to acute right ventricular infarction. Right ventricular infarcted area was evaluated by epicardial mapping ECG and myocardial regional blood flow. It was found that in the cases using IABP, the effect of reducing the infarcted area due to diastolic augmentation was noted, but the effect on the right ventricular support was not satisfactory, while in the cases using RVAD, the right ventricular preload was reduced and the right ventricular stroke work was decreased, and the effect of reducing the infarcted area was observed. But hemodynamic effect of these method were not satisfactory, enough to assist recovery from cardiogenic shock.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous kissing stents for the treatment of left main stenosis in cardiogenic shock

Significant narrowing of the left main coronary artery puts the patient at high risk, since occlusion of this vessel, if unprotected by collateral flow or a patent bypass graft to either the left anterior descending or circumflex artery, compromises flow to approximately 75% of the left ventricle. Percutaneous coronary intervention of left main coronary artery may be the only life saving procedure. There are limited data on the general use of percutaneous intervention (PCI) in patients with acute myocardial infarction (MI) due to left main disease. Small series have noted in-hospital mortality rates of 30 to 35 percent following PCI with or without stenting. Moreover, cardiogenic shock secondary to acute MI, in patients with left main coronary artery disease, carries a very high mortality. Treatment options are limited especially when emergent coronary artery bypass surgery is not an option. We report a case of emergency angioplasty of left main coronary artery with simultaneous kissing stent technique in cardiogenic shock.     

The limit of application of intraaortic balloon pumping (IABP) on canine myocardial infarction

The limit of application of intraaortic balloon pumping was evaluated in cases of canine myocardial infarction produced by either ligation of the descending coronary artery and of branches in the right coronary aretery or establishment of stenosis in the left main coronary artery. The limit of application of intraaortic balloon pumping was confirmed to be as follows: 1) stenosis of seventy-five per cent or more in left main coronary artery, 2) over 45 per cent infarction of the entire left ventricular free wall, 3) endocardial viability ratio of less than 0.65,4) blood flow of less than 18 ml/min/100g in the left circumflex coronary artery when the left descending coronary artery was ligated, 5) and less than 0.69 in the ratio of inside blood flow to outside of the left ventricular free wall, as related to regional myocardial blood flow.     

Successful surgical management of left ventricular free wall rupture in the course of myocardial infarction

The case of a 49-year-old patient is described who presented with cardiogenic shock and electrocardiographic signs of an inferolateral Q-wave infarction, and who received systemic lysis with anisoylated plasminogen streptokinase activator complex (Eminase). After coronary angiography had revealed only peripheral occlusion of a posterolateral branch of the left circumflex coronary artery, a pericardial effusion surrounding both right and left ventricular cavity was identified by echocardiography and was successfully drained via an inferior pericardiotomy with an immediate rise of blood pressure. Upon thoracotomy myocardial rupture was detected in the infarct area and was closed with mattress sutures. A total of 39 cases of successful surgical repair of myocardial free wall rupture reported in the literature is discussed. The mean age of patients was 59.6 +/- 1.3 years. Posterior and anterolateral infarctions were the preferred locations of myocardial rupture. Rupture occurred with a mean delay of 5.0 +/- 1.0 days after the onset of clinical infarct signs. Among patients saved by surgical means were 33 males and 6 females.     

绵羊左心衰竭模型的建立

目的通过选择性结扎绵羊冠状动脉对角支,以获得稳定的心力衰竭动物模型。方法对4只绵羊从心尖至心底大约40%处结扎冠状动脉对角支,在结扎前、结扎后30min和7d观察血流动力学指标的变化,作彩色超声心动图检查,记录心电图,评价心功能;然后处死绵羊,作心肌病理检查。结果4只绵羊均存活。结扎后30min和7d主动脉收缩压、心排血量较结扎前降低,肺动脉收缩压、肺毛细血管楔压和中心静脉压较结扎前均升高;超声心动图检查显示左心室舒张期末内径、左心室收缩期末内径较结扎前增大,左心室射血分数、左心室缩短分数较结扎前降低(P<0.05)。结论通过选择性结扎绵羊冠状动脉对角支可以获得稳定、可靠的左心衰竭动物模型。     

In vitro comparison of support capabilities of intra-aortic balloon pump and Impella 2.5 left percutaneous

The Impella 2.5 left percutaneous (LP), a relatively new transvalvular assist device, challenges the position of the intra-aortic balloon pump (IABP), which has a long record in supporting patients after myocardial infarction and cardiac surgery. However, while more costly and more demanding in management, the advantages of the Impella 2.5 LP are yet to be established. The aim of this study was to evaluate the benefits of the 40 cc IABP and the Impella 2.5 LP operating at 47,000 rpm in vitro, and compare their circulatory support capabilities in terms of cardiac output, coronary flow, cardiac stroke work, and arterial blood pressure. Clinical scenarios of cardiogenic preshock and cardiogenic shock (CS), with blood pressure depression, lowered cardiac output, and constant heart rate of 80 bpm, were modeled in a model-controlled mock circulation, featuring a systemic, pulmonary, and coronary vascular bed. The ventricles, represented by servomotor-operated piston pumps, included the Frank-Starling mechanism. The systemic circulation was modeled with a flexible tube having close-to-human aortic dimensions and compliance properties. Proximally, it featured a branch mimicking the brachiocephalic arteries and a physiological correct coronary flow model. The rest of the systemic and pulmonary impedance was modeled by four-element Windkessel models. In this system, the enhancement of coronary flow and blood pressure was tested with both support systems under healthy and pathological conditions. Hemodynamic differences between the IABP and the Impella 2.5 LP were small. In our laboratory model, both systems approximately yielded a 10% cardiac output increase and a 10% coronary flow increase. However, since the Impella 2.5 LP provided significantly better left ventricular unloading, the circulatory support capabilities were slightly in favor of the Impella 2.5 LP. On the other hand, pulsatility was enhanced with the IABP and lowered with the Impella 2.5 LP. The support capabilities of both the IABP and the Impella 2.5 LP strongly depended on the simulated hemodynamic conditions. Maximum hemodynamic benefits were achieved when mechanical circulatory support was applied on a simulated scenario of deep CS.     

Temporal factors in the reduction of myocardial infarct volume by methylprednisolone.

With a canine model of myocardial infarction [ligation of the left anterior descending (LAD) coronary artery] and an intracellular stain for lactic dehydrogenase (LDH) to directly measure size of infarction, the influence of 30 mg. per kilogram of methylprednisolone sodium succinate was evaluted. The intravenous administration of a pharmacologic dose of methylprednisolone one, 2, or 3 hours after the onset of myocardial infarction significantly reduced the ultimate extent of myocardial necrosis, with the greatest reduction seen following the injection of the drug one hour after ligation. The left atrial pressure was significantly decreased by corticosteroid administration, whereas the cardiac index and peripheral vascular tone were improved insignificantly. Inconsistent and/or insignificant effects were observed in the systemic and coronary sinus blood gases and in those indices of myocardial metabolism which were determined. The potential impact of these findings on the clinical applicability of methylprednisolone sodium succinate in acute myocardial ischemia is discussed.     

Off-pump coronary artery bypass grafting for restenosis after coronary angioplasty in the patient with left main shock syndrome

A case of left main shock syndrome due to total occlusion of left main trunk was reported. A 65-year-old man with acute myocardial infarction developed cardiogenic shock shortly after admission. An emergency coronary angiogram revealed total occlusion of the left main trunk without collaterals. Immediately, a stent was implanted in the left main trunk and the lesion was successfully improved. However, the left coronary angiogram revealed 90% restenosis of the left main trunk in a coronary angiogram examined 6 months after stent placement. Since the patient suffered from poor cardiac function, off-pump coronary artery bypass grafting (left internal thoracic artery to left descending coronary artery) was successfully performed using an intracoronary shunt. No complications were observed.     

Cardiovascular parameters after acute myocardial infarction and streptokinase administration in patients receiving coronary artery bypass grafts

In 16 patients requiring coronary artery bypass grafting (10 control and 6 streptokinase patients), we compared the preoperative, operative, and postoperative cardiovascular parameters. Streptokinase patients had an acute myocardial infarction and attempted reperfusion with streptokinase before coronary artery bypass grafting. One patient failed to recannalize with streptokinase and one patient had reocclusion after withdrawal of heparin necessitating coronary artery bypass grafting. Examination of hemodynamic parameters revealed a lower preoperative mean blood pressure and an elevated pulmonary artery wedge pressure in streptokinase patients. The elevated pulmonary artery wedge pressure persisted through the postoperative period of observation. These results indicate that only minor differences exist between control and streptokinase patients. Emergency and elective coronary artery bypass grafting can be safely performed in patients treated with streptokinase for acute myocardial infarction without associated cardiogenic shock.     

A case of extended myocardial infarction treated with the left ventricular assist device (LVAD) before and after the operation--the value and limitation of LVAD

A left ventricular assist device (LVAD) was applied to a patient who had profound left ventricular failure following extended myocardial infarction caused by the left main trunk obstruction. The patient was a 61-year-old man, who had severe chest distress and was admitted 11 hours after the onset of the symptom. At the time of admission, he was already in cardiogenic shock. The emergent coronary angiography showed complete obstruction of the left main trunk and the intact right coronary artery which had no collateral flow to the left coronary artery. The intraaortic balloon pumping (IABP) was started bu could not maintain the satisfied circulation. Then a LVAD was applied to the patient 5 days after the onset. The LVAD maintained the normal circulation and prohibited exaspiration of organ failure. 19 days after the onset, scartectomy and A-C bypass to LAD was performed. The patient could not be weaned from LVAD and died of right ventricular failure following ventricular arrhythmia 20 days after the installation of LVAD. The use of LVAD for nonoperative cardiogenic shock is rare. Circulatory support with a LVAD in the treatment of a patient in cardiogenic shock following a acute myocardial infarction was considered useful.     

The Safety of Simultaneous Arterial and Coronary Sinus Perfusion: Experimental Background and Initial Clinical Results

Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients. Experimental: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mUmin with normal blood (37°C) before and after 30 minutes of perfusion with either warm (37°C) or cold (4°C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end-systolic elastance (conductance catheter) and preload recruitable stroke work Index 101%± 3% and 109%± 90%, respectively. Clinical: Simultaneous arteriaVcoronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG + valve replacementlrepair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 ± 4 minutes (range 30 to 207), with 3.5 ± 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantationhepair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm non-cardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality). Conclusion: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies. (J Card Surg 1994;9:15–25)     

A comparative evaluation of pulmonary artery balloon counterpulsation and a centrifugal flow pump in an experimental model of right ventricular infarction

To compare the efficiency of pulmonary artery balloon counterpulsation and a centrifugal flow pump in reversing the hemodynamic consequences of acute right-sided heart failure, we employed both devices in 14 Yorkshire pigs in which right ventricular infarction was created via surgical ligation of branches of the right coronary artery. Pulmonary artery balloon counterpulsation improved some of the indicators of right heart failure, as manifested by significantly decreased right atrial pressure and increased mean systemic blood pressure. In contrast, the centrifugal flow pump consistently and significantly reversed all of the hemodynamic consequences of right ventricular infarction. In comparison to pulmonary artery balloon counterpulsation, the centrifugal flow pump resulted in lower right atrial pressures (p=0.020), lower mean pulmonary pressures (p less than 0.0001), increased left atrial pressures (p=0.026), increased cardiac output (p less than 0.0001), and increased mean systemic blood pressures (p less than 0.0001). Possible mechanisms to explain the superiority of the centrifugal flow pump include better hemodynamic unloading of the failing myocardium and independence from right ventricular output.     

Alterations in collateral blood flow produced by isoflurane in a chronically instrumented canine model of multivessel coronary artery disease

The actions of isoflurane and adenosine on left ventricular myocardial perfusion during a total occlusion of the left anterior descending coronary artery and concomitant stenosis of the left circumflex coronary artery were investigated in dogs chronically instrumented for measurement of systemic and coronary hemodynamics, regional myocardial contractile function (via ultrasonic sonomicrometers), and myocardial blood flow (via the radioactive microsphere technique). An Ameroid constrictor was implanted on the left circumflex coronary artery to produce a slowly progressive stenosis that gradually depleted the coronary reserve of the distal vascular bed. The reductions in reserve were evaluated by daily measurement of baseline left circumflex coronary blood flow velocity and the hyperemic response to injection of adenosine. At a stage of moderate or severe left circumflex stenosis development, the left anterior descending coronary artery was totally occluded via a hydraulic occluder to simulate multivessel coronary artery disease, and control measurements of hemodynamics, regional contractile function, and myocardial blood flow were completed. In separate groups of experiments, either adenosine (0.64 and 1.28 mg/min) or isoflurane (1.6-1.8 and 2.3-2.5%, end-tidal) was administered and measurements remade during steady state hemodynamic conditions. Finally, diastolic aortic pressure and heart rate were adjusted to levels present in the control state during administration of adenosine or isoflurane, and additional measurements were recorded. Isoflurane reduced mean arterial pressure, left ventricular systolic pressure, and the rate of increase of left ventricular pressure at 50 mmHg (positive dP/dt50) without change in heart rate. Administration of isoflurane decreased blood flow in normal, stenotic, and occluded regions; however, when arterial pressure and heart rate were restored to levels present in the conscious state, myocardial perfusion in all regions was maintained at control levels. Ratios of flow between occluded and normal or stenotic zones remained unchanged from the conscious state during a constant aortic pressure and heart rate. Similar results were obtained in dogs with either a moderate or severe left circumflex coronary artery stenosis. In contrast, adenosine produced a dose-related decrease in collateral flow and occluded-to-normal or occluded-to-stenotic zone flow ratio. The results of this investigation indicate that adenosine but not isoflurane redistributes blood flow away from collateral-dependent myocardium to other regions in a chronically instrumented canine model of multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS)