Levels Of Coronary Perfusion Pressure Research Articles

Automated pupillometry helps monitor the efficacy of cardiopulmonary resuscitation and predict return of spontaneous circulation.

We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA). Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO2), regional cerebral tissue oxygen saturation (rSO2) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR. ROSC was achieved in 11/16 animals. The levels of CPP, ETCO2, rSO2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46-0.78, all P < 0.001). Furthermore, comparable performance was also achieved by automated pupillometry (AUCs of Init, End and %PLR were 0.821, 0.873 and 0.821, respectively, all P < 0.05) compared with the traditional indices (AUCs = 0.809-0.946). The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest.

Abstract 262: Hemodynamically-Guided Optimum Chest Compression Point in a Rat Model of Cardiopulmonary Resuscitation

Introduction: CPR aims to re-establish blood flow by chest compression (CC), achieving threshold levels of coronary perfusion pressure (CPP). For this, current guidelines recommend the lower sternal half as optimum CC point. However, this point might be not optimal for every individual. We investigated the hemodynamics generated by CC performed on different chest points in a rat model of CPR. We hypothesized that a CC point hemodynamically-identified would be a better approach compared to the lower sternal half. Methods: Ten male rats were anesthetized and arterial and right atrial pressures monitored. Ventricular fibrillation was induced and untreated for 8 min. CPR, including mechanical CC, ventilation, and epinephrine, was then performed for 8 min. Animals were divided to receive CC performed either on the lower sternal half (standard (STD), n=5) or on an optimum point identified as the one able to generate the maximum CPP (MaxCPP group, n=5). Cardiac districts involved in CC were subsequently identified by computed tomography (CT). Results: STD CC produced a CPP that was constantly below the threshold for successful resuscitation and trended to decrease over time. When the optimum CC point was identified hemodynamically, the CPP generated was constantly &gt; 20 mmHg. Indeed, CPP was significantly higher in the MaxCPP group compared to the STD one for the whole 8 min of CPR (p&lt;0.01, Fig). Moreover, administration of epi rapidly further improved CPP (p&lt;0.01 vs. pre-epi) in the group with an optimized CC point, while no drug effect was observed in the STD one. CT scan showed that the lower sternal half did not correspond to the LV maximum diameter, known to account for a maximum stroke volume generation during CC (Fig). Conclusion: Standard lower sternal half CC point is not able to maximize hemodynamics during CPR, making ineffective CC efforts and vasopressor administration. The quality of CPR may improve if the optimum CC point is identified as a reflection of CPP generated.

Activation of TP receptors induces high release of PGI2 in coronary arteries of renal hypertensive rats

AimTo investigate the molecular mechanisms and cellular signaling pathways involved in the activation of TP receptors and the consequent induction of contractile responses in coronary arteries of renal hypertensive (2K-1C) rats. Methods and resultsThe coronary perfusion pressure (CPP) was lower in 2K-1C rats during increased coronary flow as measured by the Langendorff technique. The coronary contraction and relaxation were evaluated by vascular reactivity studies, and the molecular mechanisms were investigated on the basis of the protein expression of TP receptors, Cav-1, eNOS, COX-1, and COX-2, as measured by Western blot. The levels of eicosanoids were determined by ELISA immunoassay and analyzed by reverse-phase HPLC coupled to electrospray ionization mass spectrometry (HPLC-MS/MS). The metabolites from NO production were evaluated by the Griess reaction. The coronary arteries of 2K-1C rats expressed COX-2 to a larger extent and TP receptors to a lesser extent than the coronary arteries of normotensive (2K) rats. Selective COX-1 and non-selective COX inhibitors reversed the reduction in the contraction induced by TP receptors in the coronary arteries of 2K-1C rats. U46619, an agonist of TP receptors, induced a contractile response that was relaxed by acetylcholine (ACh). In the coronary arteries of 2K-1C rats, this ACh-induced relaxation depended on COX. The activation of TP receptors increased the production of PGI2 in the coronary arteries of 2K-1C rats. The results demonstrated that increased COX signaling in the coronary arteries of 2K-1C rats mediated the low levels of CPP, the contraction induced by the activation of TP receptors, and the endothelium-dependent relaxation. The vasodilator PGI2 seemed to be the major product. ConclusionActivation of TP receptors increases production of PGI2 in coronary arteries of 2K-1C rats.

Transthoracic application of electrical cardiopulmonary resuscitation for treatment of cardiac arrest

Observational studies have shown that muscular stimulation contracting the thoracic cage may produce coronary perfusion pressures equal to manual chest compressions. This study examined electrical cardiopulmonary resuscitation for coronary perfusion pressures during ventricular fibrillation in a porcine model of cardiac arrest. Prospective randomized controlled study. University affiliated research institute. Domestic male pigs. In seven domestic male pigs (40 +/- 2 kg), ventricular fibrillation was induced electrically and untreated for 10 secs. For each ventricular fibrillation episode, one of 16 electrical cardiopulmonary resuscitation stimulation protocols (pulse trains) or manual chest compression was applied. Each compression protocol was applied for 20 secs, followed by a defibrillation shock. The experimental procedure was performed across one or more randomized complete blocks. The electrical cardiopulmonary resuscitation pulse trains were defined by four two-level factors: pulse width (0.15 and 7.5 msec), pulse period (15 and 30 msec), train width (50 and 200 msec), and train rate (60 or 120 compressions per min). Pulse trains comprised two groups, based on pulse width (skeletal-based, 0.15 msec; cardiac-based, 7.5 msec). Train width was the significant design parameter for producing efficacious levels of coronary perfusion pressures for the skeletal-based electrical cardiopulmonary resuscitation pulse trains (p = 0.02). Both train width and train rate were significant design parameters for producing efficacious levels of coronary perfusion pressures for the cardiac-based electrical cardiopulmonary resuscitation pulse trains (p < 0.001, p = 0.5, respectively). Optimal skeletal-based and cardiac-based electrical cardiopulmonary resuscitation pulse trains were significantly better than ventricular fibrillation (p = 0.01, p = 0.01, respectively) and equivalent to manual chest compression (p = 0.2, p = 0.7, respectively) for sufficient coronary perfusion pressure levels. Optimal skeletal-based and cardiac-based electrical cardiopulmonary resuscitation pulse train parameters generated levels of coronary perfusion pressure significantly greater than ventricular fibrillation and comparable with manual chest compression over a short interval of untreated cardiac arrest.

Abstract 2059: Transthoracic Application of Medium Voltage Therapy Maintains Forward Blood Flow during Cardiac Arrest

We have previously reported that transthoracic medium voltage therapy (MVT) generated coronary perfusion pressure (CPP), forward carotid blood flow (CBF) and end-tidal CO 2 (EtCO 2 ) comparable to those produced by manual chest compression. In the present study, we investigated the capability of MVT to generate and maintain forward blood flow for a longer interval, i.e. 1 min, in a porcine model of short duration cardiac arrest. MVT can maintain threshold levels of CPP, CBF and EtCO 2 , for a minute interval prior to defibrillation. In 7 domestic male pigs weighing 40 ± 1 kg, VF was electrically induced and untreated for 10 seconds. Animals were then subjected to receive MVT for one minute with the aid of a Galvani E-CPR device (Galvani Ltd, Edina, MN), after when a biphasic shock was delivered. The MVT pulsed packet was 400 msec, the pulsed packet rate was 80/min, the intra-packet pulse period was 25 ms and intra-packet pulse durations were 0.2 ms. CPP and EtCO2 were continuously measured during MVT. CBF and ejection fraction generated during MVT were measured by echo-Doppler technique, while cardiac output with stroke volume by thermodiluition method. MVT was able to maintain CPP and EtCO2 above the threshold levels for successful resuscitation for the entire interval of application (Table ). During MVT, excellent stroke volume, cardiac output and ejection fraction together with carotid blood flow were generated (Table ). MVT produced and maintained for one minute forward blood flow during cardiac arrest. This electrical therapy might represent a new approach intended to generate and/or maintain forward blood flow in lieu of or in association with chest compression in victims of cardiac arrest

Cardiopulmonary arrest and resuscitation in Landrace/Large White swine: a research model

Sudden cardiac death (SCD) is a field of continuous research. In order to answer various questions regarding SCD, several animal models have been developed. The aim of the present study is to describe our experimental model of inducing cardiac arrest in Landrace/Large White pigs, and then resuscitated according to the International Guidelines on resuscitation. Fifteen Landrace/Large White pigs were anaesthetized and intubated while spontaneously breathing. The left and right jugular veins, as well as the femoral and the carotid arteries, were surgically prepared. Induction of cardiac arrest was achieved by using an ordinary rechargeable lithium battery, through a pacemaker wire inserted into the right ventricle. The typical Advanced Life Support (ALS) protocol was followed, and in case of restoration of spontaneous circulation, the animals were further evaluated for 30 min. Seven animals were successfully resuscitated using this protocol, whereas eight failed resuscitation efforts. Successful resuscitation was contingent on the restoration of the levels of coronary perfusion pressure and PETCO(2) during chest compressions. Among the different ways of inducing cardiac arrest, the ordinary lithium battery is a simple, safe and valuable technique. Landrace/Large White pigs' baseline haemodynamics closely resemble human haemodynamics, making the breed a favourable model for resuscitation.

Challenging the rationale of three sequential shocks for defibrillation

The 2000 guidelines for cardiopulmonary resuscitation (CPR) recommend up to three sequential shocks for persistent ventricular fibrillation (VF). We hypothesized that the time consumed for repetitive rhythm analyses and recharging of the capacitor compromises the success of the second and third shock of each sequence. In 60 domestic pigs, VF was electrically induced and untreated for 7 min. After 1 min of CPR, which includes precordial compression and ventilation, up to three sequential shocks were delivered. All animals were resuscitated. For purposes of the present study we determined the outcomes of the first, the second, and the third shock of each sequence during attempted defibrillation. Our criterion of success was the restoration of spontaneous circulation (ROSC). Forty-eight of the 60 animals (80%) attained ROSC after the first shock, 9/60 (15%) after the second shock, and only 3/60 (5%) after the third shock. In confirmation of the earlier observations, ROSC was highly predictive when the coronary perfusion pressure (CPP) exceeded 12 mmHg and end-tidal CO(2) (ETCO(2)) exceeded 11 mmHg. However, these criteria were never achieved after the second shock. The present study supports the rationale of delivering only a single shock, or at the most two shocks, prior to resuming chest compression, to re-establish the threshold levels of CPP and ETCO(2) before delivery of a subsequent electrical shock.

Miniaturized chest compressor

Current American Heart Association guidelines call for continuous manual chest compressions for cardiopulmonary resuscitation. Chest compressions maintain critical levels of forward blood flow, including blood flow to the myocardium during cardiac arrest, to allow for successful resuscitation. The demand on rescuers is to ensure that compression is consistent, with appropriate force and depth, often under difficult conditions of rescue, evacuation, and transport. It is also of great moment that fatigue of the rescuer adversely affects outcomes. This evaluation was to compare two pneumatically driven devices, the Michigan Thumper (Michigan Instruments, Grand Rapids, MI), as an industrial standard, and the miniaturized chest compressor. On a porcine model of cardiopulmonary resuscitation, alternating current fibrillation was induced for 7 mins, followed by 5 mins of chest compression. Arterial and right atrial pressures and end-tidal CO2 were measured. Coronary perfusion pressure was calculated as the difference between compression end-diastolic arterial pressure and right atrial pressure. Threshold levels of coronary perfusion pressure (>15 mm Hg) and end-tidal CO2 (>10 mm Hg) for successful defibrillation were maintained with the miniaturized chest compressor. Consistently greater coronary perfusion pressure and end-tidal CO2 values were achieved with the miniaturized chest compressor in comparison with the Thumper. The miniaturized chest compressor has the important potential advantage of minimal weight and, therefore, portability, without any reduction in effectiveness. To the contrary, it is potentially more effective than the much larger and heavier industry standard for maintaining circulation.

Preoperative cardiology consultation.

In a 1998 survey of New York metropolitan area anesthesiologists, surgeons, and cardiologists, the three specialties were in general agreement that important purposes of a cardiology consultation are to treat an inadequately treated cardiac condition before surgery (e.g., unstable angina or congestive heart failure [CHF]), to provide data to use in anesthesia management (e.g., ischemic threshold of tachycardia on stress test or left ventricular ejection fraction), and possibly to diagnose a medical condition before surgery (e.g., the cause of a new-onset atrial fibrillation). The yield of a cardiology consultation, in terms of new therapy or significant effect on patient management strategy prior to surgery, has, however, been reported to vary widely from 10% to more than 70%. The reasons why the consultation process often falls short of ideal are probably multifold, but may often originate from vague understanding of the consultation process. The physician initiating the consultation, whether an anesthesiologist or a surgeon, may not make it clear to the cardiologist why the consultation is being sought. In a retrospective review of 202 cardiology consultations at a university hospital, it was found that 108 just asked for an “evaluation,” 79 asked for a “clearance,” and 9 did not specifically request anything. Only six posed a specific question. As a result, the consultant often makes broadly inclusive, general remarks about perioperative management of the patient and may recommend preoperative diagnostic work-up that does not influence the patient’s outcome but prolongs the hospital stay. In this review are presented (1) the indications for cardiology consultations as implied in the American College of Cardiology–American Heart Association (ACC–AHA) guidelines on preoperative cardiac evaluation, and (2) suggestions on how the ACC–AHA guidelines may be critically applied to, and improve, the consultation process. Preoperative Cardiac Consultation Based on the ACC–AHA Guidelines The ACC–AHA guidelines on preoperative cardiac evaluation were published initially in 1996 and were also endorsed by the Society of Cardiovascular Anesthesiologists and the Society for Vascular Surgery. An updated version of the guidelines was published in 2002. The guidelines were based on the then-available literature as well as expert opinions from the disciplines of anesthesiology, cardiology, electrophysiology, vascular medicine, vascular surgery, and noninvasive cardiac testing. The guidelines provided an 8-step algorithm for stratifying the patient’s risks and triaging to either surgery or cardiac evaluation. The first three steps of the guidelines consider the urgency of the operation and the recency of cardiac evaluation and intervention. If the operation is not emergent and if there has not been recent cardiac evaluation and/or intervention with no significant interim changes, then the remainder of the guidelines are applied. Steps 4 through 7 deal with an assessment of the patient’s clinical predictors of cardiac risk, functional status, and the risk of the surgery proposed. Step 8, or noninvasive cardiac testing to further define the patient’s risk, is indicated (1) if the patient has a major clinical predictor, (2) if the patient has an intermediate clinical predictor and either has poor functional status or is undergoing a high-risk surgery, or (3) if the patient has poor functional status and is undergoing a high-risk surgery. As defined by the ACC–AHA, major clinical predictors are unstable coronary syndrome, decompensated congestive heart failure (CHF), significant arrhythmias, and severe valvular disease. Intermediate clinical predictors are mild angina pectoris, history of myocardial infarction (MI) or CHF, diabetes mellitus, and chronic renal failure with serum creatinine greater than 2 mg/dl. A high-risk surgery carries a greater than 5% perioperative risk of cardiac events such as MI, CHF, or death and is exemplified by emergent major operations, especially in the elderly, aortic, and other major vascular procedures, peripheral vascular bypass procedures, and anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss. An intermediate-risk surgery carries 1–5% perioperative risk of cardiac events and is exemplified by carotid endarterectomy, intraperitoneal and Director of Vascular Anesthesia, Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, and Associate Professor of Anaesthesia, Harvard Medical School.

Cardiopulmonary resuscitation in the mouse.

We sought to develop a model of cardiac arrest and resuscitation on mice that would be comparable to that of large mammals and would allow for more fundamental investigations on cardiopulmonary arrest and cardiac resuscitation. A model of cardiopulmonary resuscitation previously developed by our group on rats was adapted to anesthetized, mechanically ventilated adult male Institute of Cancer Research mice that weighed 46 +/- 3 g. The trachea was intubated through the mouth, and end-tidal PCO(2) (PET(CO(2))) was measured with a microcapnometer. Catheters were advanced into the aorta and into the right atrium, and coronary perfusion pressure (CPP) was computed. A 1.5-mA alternating current was delivered to the right ventricular endocardium, which produced ventricular fibrillation or a pulseless rhythm. Precordial compression was begun 4 min later. Ten sequential studies were performed, during which five animals were successfully resuscitated and five failed resuscitation efforts. Successful resuscitation was contingent on the restoration of threshold levels of CPP and PET(CO(2)) during chest compression. As in rats, swine, and human patients, threshold levels of mean aortic pressure, CPP, and PET(CO(2)) were critical determinates of resuscitability in this murine model of threshold level of cardiac arrest and resuscitation.

Adverse Outcomes of Interrupted Precordial Compression During Automated Defibrillation

Current versions of automated external defibrillators (AEDs) require frequent stopping of chest compression for rhythm analyses and capacity charging. The present study was undertaken to evaluate the effects of these interruptions during the operation of AEDs. Ventricular fibrillation was electrically induced in 20 male domestic swine weighing between 37.5 and 43 kg that were untreated for 7 minutes before CPR was started. Defibrillation was attempted with up to 3 sequential 150-J biphasic shocks, but each was preceded by 3-, 10-, 15-, or 20-second interruptions of chest compression. The interruptions corresponded to those that were mandated by commercially marketed AEDs for rhythm analyses and capacitor charge. The sequence of up to 3 electrical shocks and delays were repeated at 1-minute intervals until the animals were successfully resuscitated or for a total of 15 minutes. Spontaneous circulation was restored in each of 5 animals in which precordial compression was delayed for 3 seconds before the delivery of the first and subsequent shocks but in none of the animals in which the delay was >15 seconds before the delivery of the first and subsequent shocks. Longer intervals of CPR interventions were required, and there was correspondingly greater failure of resuscitation in close relationship to increasing delays. The durations of interruptions were inversely related to the durations of subthreshold levels of coronary perfusion pressure. Postresuscitation arterial pressure and left ventricular ejection fraction were more severely impaired with increasing delays. Interruptions of precordial compression for rhythm analyses that exceed 15 seconds before each shock compromise the outcome of CPR and increase the severity of postresuscitation myocardial dysfunction.

Effect of arrest time on the hemodynamic efficacy of precordial compression: Crit Care Med 1995; 23/7: 1233–1236

Objectives : To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO 2 as predictors of resuscitability after prolonged cardiac arrest. Design : Prospective, randomized, controlled animal study. Setting : University research laboratory. Subjects : Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. Interventions : Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. Measurements and Main Results : All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO 2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. Conclusions : The efficacy of precordial compression-as measured by coronary perfusion pressure and end-tidal CO 2 concentration after prolongation of untreated cardiac arrest- was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO 2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest. (Crit Care Med 1995 ; 23 :1233-1236)

Effect of arrest time on the hemodynamic efficacy of precordial compression

To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest. Prospective, randomized, controlled animal study. University research laboratory. Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.

Augmented efficacy of external CPR by intermittent occlusion of the ascending aorta.

After prolonged cardiac arrest, conventional methods of closed-chest cardiac compression are ineffective. This is primarily because of failure to generate minimal threshold levels of coronary perfusion pressure for cardiac resuscitation. This report introduces a new option for cardiac resuscitation by use of a combination of intermittent ascending aortic balloon occlusion, aortic infusion, and precordial compression to increase the pressure gradient for coronary perfusion. Twenty anesthetized, mechanically ventilated, normovolemic domestic pigs were investigated. A 10F balloon catheter was advanced from the left femoral artery into the ascending aorta. Ventricular fibrillation was induced with an AC current delivered through an electrode catheter advanced into the right ventricle. Precordial compression was initiated after 7 minutes of untreated ventricular fibrillation. The animals were randomized to one of four groups: (1) balloon occlusion with proximal infusion of oxygenated saline, (2) balloon occlusion alone, (3) proximal aortic infusion together with epinephrine without balloon occlusion, and (4) injection of epinephrine without balloon occlusion or proximal infusion. For balloon occlusion, the balloon was inflated for 30 seconds during each minute of cardiopulmonary resuscitation. In the subsets of animals that received infusions, oxygenated saline (30 mL) was injected into the proximal aorta immediately after balloon occlusion. Epinephrine was used in two subsets: It was injected as a bolus in amounts of 30 micrograms/kg into the right atrium at 30 seconds after start of precordial compression and repeated as required to maintain coronary perfusion pressure within the range of 25 to 30 mm Hg. Defibrillation was attempted at 1 minute after start of precordial compression and at 1-minute intervals thereafter. Resuscitation attempts were continued until there was return of spontaneous circulation or for a total of 30 minutes after start of precordial compression. Coronary perfusion pressure generated by precordial compression was significantly increased after balloon occlusion. Each of 10 animals was successfully resuscitated and survived for 48 hours after balloon occlusion whether or not it was combined with infusion. Three of five animals were resuscitated by a combination of infusion and epinephrine in the absence of aortic occlusion, but none survived for 48 hours (P = .02). Only one epinephrine-treated animal was successfully resuscitated and survived for 48 hours in the absence of balloon occlusion or infusion (P < .05). Ascending aortic balloon occlusion with or without proximal aortic infusion strikingly increased resuscitability and 48-hour survival after cardiac arrest under conditions when conventional methods failed.

Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium.

These experiments tested the hypothesis that differences in the distribution of subepicardial and subendocardial microvascular resistances may alter the transmural distributions of microvascular pressures. Isolated blood- and physiological saline-perfused porcine hearts were surgically incised to enable exposure of the subendocardial and subepicardial microcirculations. Microvascular pressures were measured during cardiac arrest and maximal vasodilation at various perfusion pressures to formulate relations between perfusion pressure and microvascular pressure in the different subendocardial (both free wall and papillary muscle) and subepicardial segments. Measurements of arteriolar and venular pressures in both myocardial regions were performed in comparably sized vessels (80-120 microns in diameter). At a coronary perfusion pressure of 100 mm Hg, subendocardial arteriolar and venular pressures were 60 +/- 4 and 33 +/- 3 mm Hg, respectively. In contrast, at the same coronary perfusion pressure, arteriolar and venular pressures in the subepicardial microcirculation averaged 80 +/- 6 and 22 +/- 3 mm Hg, respectively (p less than 0.05 versus subendocardium). At all levels of coronary perfusion pressure, arteriolar pressures were significantly lower in the subendocardium than in the subepicardium (p less than 0.05). Venular pressures were also higher in the subendocardial microcirculation than in the subepicardial microcirculation at all but the lowest perfusion pressure (p less than 0.05). The relative distribution of resistances in arteries, microvessels, and veins was also different between the subepicardium and subendocardium. Specifically, in the subendocardium, arterial and venous resistances were higher, percentage-wise, but microvascular resistance was proportionately lower than that in the subepicardium (p less than 0.05). From these data, it is concluded that the distribution of microvascular resistances and pressures is different during maximal vasodilation in the subepicardial and subendocardial microcirculations of the left ventricle. It is also speculated that differences in autoregulatory capacity and vulnerability to ischemia may be partially related to unequal distribution of microvascular resistances across the wall of the left ventricle.

Homogeneous distribution and pressure dependent reduction of coronary blood flow in right ventricular free wall during coronary hypoperfusion in anaesthetised open chest dogs.

Relationship of coronary perfusion pressure with total and regional myocardial blood flow in right ventricular free wall was studied in 10 anaesthetised open chest dogs. The right coronary artery was perfused by an autoperfusion system from the carotid artery. Total coronary blood flow into the perfused area was measured by an extracorporeal electromagnetic flow probe. Critical perfusion pressure of the right coronary artery, defined as the lowest pressure level below which the regional wall motion deteriorated, was 39(SEM1) mm Hg. Reactive hyperaemia was noted at 60(2) mm Hg, a level well above the critical perfusion pressure. There was an inverse linear relation between the level of reactive hyperaemia and perfusion pressure. Regional myocardial blood flow was measured by a tracer microsphere technique at control condition, just above and below the critical perfusion pressures and during coronary occlusion. This correlated closely with values obtained by an electromagnetic flow probe (r = 0.94, p less than 0.001) and both values were dependent on the level of perfusion pressure. Endocardial to epicardial flow ratio remained at unity at any level of coronary perfusion pressure. Thus the level of coronary perfusion pressure was a major determinant of the regional myocardial blood flow into the right coronary artery, and autoregulation of the regional myocardial blood flow was not apparent across the wall, despite the presence of a reactive hyperaemia.

Myocardial energetics: experimental and clinical studies to address its determinants and aerobic limit.

The major determinants of myocardial oxygen consumption (MVO2) were examined in the isolated, servo-regulated, canine heart in which coronary perfusion pressure, heart rate, ventricular volume and pressure could be individually monitored and controlled. We found that the integral of systolic wall force and the time derivative of systolic force development were major determinants of MVO2, Net MVO2, seen in response to increments in contractility (dobutamine) and heart rate, were the result of the relative increments in each of these determinants. Additional studies were performed to assess the heart's metabolic reserve and aerobic limit (i.e., before the onset of lactate production). We found that with increments in left ventricular work, mediated by increments in filling volume, heart rate, and contractility (dobutamine), myocardial lactate production could be induced, but was dependent on the level of coronary perfusion pressure. When the aerobic limit of the myocardium was exceeded, its performance declined and pulsus alternans appeared. In patients with cardiomegaly and advanced heart failure given the phosphodiesterase inhibitors enoximone and piroximone we did not observe a rise in MVO2 or the appearance of lactate production in the majority of patients. When patients with documented idiopathic (dilated) cardiomyopathy and marked heart failure received hemodynamically significant doses of dobutamine alone or in combination with amrinone, there again was no evidence of lactate production or a rise in MVO2, while a marked improvement in ventricular function was noted. Thus, these agents served to improve the efficiency of the dilated failing heart. Hence we would conclude that in most cases, the dilated failing heart has an adequate metabolic reserve. It performance, and indeed its efficiency, can be improved with pharmacologic agents having positive inotropic properties without adversely altering myocardial energetics.

Pressure-dependent vasoactive effects of histamine in the coronary circulation.

Twenty-one isolated, perfused, spontaneously rhythmic guinea pig hearts (Langendorff preparation) were used to investigate the effects of coronary perfusion pressure (CPP) on the coronary vasoactive response to a continuous infusion of histamine. Heart rate (HR), coronary perfusate flow (CPF), left ventricular pressure, dp/dtmax, oxygen extraction, and myocardial oxygen consumption (MVO2) were measured at constant CPP of 40 (n = 9), 53 (n = 6), and 65 cm H2O (n = 6) in the absence and presence of continuous intracoronary infusion of histamine [0.9 +/- 0.2 microgram/(min X g)]. At 40 cm H2O histamine caused significant coronary vasodilation. At 65 cm H2O histamine caused significant coronary vasoconstriction. At an intermediate pressure of 53 cm H2O histamine had no effect on CPF. At all three pressures HR, left ventricular pressure, dp/dtmax, and oxygen extraction increased significantly in response to histamine. MVO2 was unchanged by histamine at 65 cm H2O (flow was reduced but extraction increased. MVO2 increased modestly but significantly at 53 cm H2O (12% increase; flow unchanged but extraction increased), and increased prominently at 40 cm H2O (50% increase; flow and extraction increased). We conclude that the coronary vascular effects of continuously infused histamine are dependent on the preexisting, steady-state level of CPP in the isolated perfused guinea pig heart.

Effects of Nitroglycerin on Regional Myocardial Function in the Underperfused Canine Heart

Effects of nitroglycerin (3 micrograms/kg/min i.v.) on regional myocardial contractility during acute coronary stenosis were studied in open-chest dogs using a strain-gauge arch. Stenosis-induced stepwise decreases in coronary perfusion pressure (CPP) at less than 40 mm Hg correspondingly reduced contractility in the underperfused area and increased the left ventricular end-diastolic pressure (LVEDP). Nitroglycerin caused significant increases in contractility, along with decreases in arterial and left ventricular pressures; at stenosis-induced CPP less than 30 mm Hg, contractility in the underperfused are fell precipitously below the control, while LVEDP increased. When nitroglycerin infusion under coronary stenosis (CPP of 40 mm Hg) decreased CPP to less than 30 mm Hg, contractility fell. When CPP greater than 30 mm Hg was maintained, contractility increased and LVEDP decreased. In conclusion, at least in the absence of well-developed collateral circulation, the critical level of CPP was 40 mm Hg for contractility and LVEDP without nitroglycerin, which shifted to 30 mm Hg with the addition of nitroglycerin. Nitroglycerin resulted in a significant increase in plasma catecholamines, and the increase in contractility diminished with propranolol, indicating participation of beta-adrenoceptor in the positive inotropic effect of nitroglycerin. However, catecholamines at high concentrations probably further aggravated the impaired cardiac function at CPP less than 30 mm Hg.

Role of afterload in determining regional right ventricular performance during coronary underperfusion in dogs.

The relationship between coronary perfusion pressure and regional myocardial performance of the right ventricular free wall was studied, in the presence or absence of right ventricular hypertension in 13 open-chest dogs. The right coronary artery was perfused through a shunt from a carotid artery. Regional systolic shortening of the right ventricular free wall was measured by means of a sonomicrometric technique at various levels of coronary perfusion pressure. Regional shortening was insensitive to coronary perfusion pressure or flow when it was above 31 mm Hg or 0.27 ml/min per g. Once coronary perfusion was below this critical level, regional shortening in both base to apex and circumferential orientations decreased linearly, depending on the degree of perfusion pressure. Despite the presence of a monoexponential relationship between coronary perfusion pressure or flow and regional shortening, a direct linear relation between perfusion pressure and flow was consistently noted, with or without pulmonary artery banding, suggesting that there is limited autoregulation of right coronary flow. The critical perfusion pressure for maintaining regional myocardial function of the right ventricle was highly dependent on the level of right ventricular systolic pressure (r = 0.64 - 0.72, P less than 0.05). Thus, right ventricular systolic pressure was one of the important determinants of regional wall motion during coronary underperfusion.