Myocardial Oxygen Delivery Research Articles

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog

We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MVo(2)) and oxygen delivery during pregnancy. Awake dogs were studied using echocardiography before and at 40 days, 50 days, and 60 days (60D) of pregnancy and at approximately 14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MVO(2) of left ventricular tissue samples was measured in vitro in response to increasing doses of bradykinin, enalapril maleate, and amlodipine. We examined the changes in passive diameter and flow-dependant arteriolar dilation of coronary arterioles. Echocardiography indicated increases in cardiac output ( approximately 60%) during pregnancy. Myocardial eNOS (21 +/- 4%), phosphorylated eNOS (19 +/- 3%), and SOD-1 (61 +/- 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10(-4) mol/l) decreased MVO(2) in a nitric oxide-dependant manner (by 24 +/- 1.3% in controls and 34 +/- 2.2% at 60D; by 21 +/- 1.1% in controls and 29 +/- 1.1 at 60D; and by 22 +/- 2.5% in controls and 26 +/- 1.0% at 60D, respectively). Arterioles from pregnant dogs showed increased flow-dependant dilation in response to increased shear stress and larger passive diameter. Nitrite production was stimulated by bradykinin and carbachol in microvessels in vitro; pregnancy enhanced nitrite release. Myocardial eNOS, phosphorylated eNOS, and SOD-1 protein expression are increased during pregnancy, and this increase is associated with enhanced nitric oxide-dependant control of MVO(2). Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.

Attenuation of ischemia reperfusion injury in failing hearts by endothelin-a receptor blockade

Objective: Ischemia/reperfusion (I/R) injury due to cardioplegic arrest is a problem in patients with reduced LV function. We investigated the effect of chronic versus acute administration of the selective endothelin-A receptor antagonist TBC-3214Na during I/R in failing hearts. Methods: Male SD rats underwent coronary ligation. 3 days post infarction group 1 (n=11) was administered TBC-3214Na continuously with their drinking water, group 2 and 3 received placebo. 7 weeks post infarction hearts were evaluated on a blood perfused working heart during 60′ ischemia and 30′ reperfusion. In group 2 (n=10) TBC-3214Na and in group 3 placebo were added to cardioplegia during ischemia. Data: At similar infarct size postischemic recovery of cardiac output (group1: 91±10%, group2: 86±11% vs. placebo: 52±15%; p<0,05) and external heart work (group1: 90±10%, group2: 85±13% vs. placebo: 51±17%, p<0,05) was significantly enhanced in group 1+2 while recovery of coronary flow was only improved in group 2 (group2: 121±23% vs. group1: 75±13%, placebo: 64±15%, p<0,05). In group 2 myocardial oxygen delivery and high energy phosphates were enhanced accompanied by a lower lactate production, and transmission electron microscopy revealed less ultrastructural damage. Conclusion: Ultrastructural and biochemical evaluation indicates an improvement in capillary perfusion only under acute TBC-3214Na administration during ischemia/reperfusion resulting in a better cardiac function post ischemia.

Cardioprotective effects of acute normovolemic hemodilution in patients with severe aortic stenosis undergoing valve replacement

After acute normovolemic hemodilution (ANH), improvement of the rheologic conditions may contribute to optimize tissue oxygen delivery and attenuate ischemia-reperfusion injuries. It was hypothesized that ANH would confer additional cardioprotection in patients with ventricular hypertrophy undergoing open heart surgery. This study was a randomized controlled trial. Forty patients scheduled for elective aortic valve replacement were randomly assigned to a control group (standard care) or an ANH group (target hematocrit level of 28%). All patients were managed with standard myocardial preservation techniques (cold blood cardioplegia, anesthetic preconditioning). The outcome measures included the release of myocardial enzymes, perioperative hemodynamic changes, the need for pharmacologic cardiovascular support, and cardiac complications. In the ANH group, the postoperative release of troponin I (mean peak plasma concentrations, 1.7 ng/mL; 95% confidence interval, 1.4-2.1 ng/mL) and myocardial fraction of creatine kinase (22 U/L; range, 18-24 U/L) was significantly lower than in the control group (3.6 [range, 3.0-4.2] ng/mL and 45 [range, 39-51] U/L, respectively). In addition, requirement for inotropic support was significantly lower and fewer hemodiluted patients presented adverse cardiac events. After ANH, there was a significant decrease in heart rate (-11 +/- 6%) and rate-pressure product (-16 +/- 8%) until the aortic cross-clamping time and, at the end of surgery, the circulating levels of erythropoietin (EPO) were higher than in control patients (13.6 +/- 4.2 mUI/mL vs. 7.3 +/- 2.4 mUI/mL; p < 0.05). Besides conventional cardiac preservation techniques, preoperative ANH further attenuates myocardial injuries. Optimization of preischemic myocardial oxygen delivery and/or consumption and the postconditioning effects of endogenous EPO are potential mechanisms for ANH-induced cardioprotection.

The Effect of Phenylephrine on Cardiac Performance and Myocardial Oxygen Balance in Resuscitation from Hemorrhagic Shock

Background: The issue of using phenylephrine in hemorrhagic shock treatment has been controversial because it is known that phenylephrine improves the tissue perfusion by increasing arterial blood pressure but deteriorates the myocardium by increasing afterload and decreasing myocardial oxygen delivery via coronary vasoconstriction. This study was aimed to assess the effects of phenylephrine on hemodynamic variables, cardiac performance, and myocardial oxygen balance in resuscitation from hemorrhagic shock. Methods: Twenty anesthetized dogs were randomly divided into phenylephrine group and control group. After inducing hemorrhagic shock, resuscitation was done with phenylephrine and 0.9% normal saline respectively. We measured hemodynamic indices, blood gas parameter and cardiac enzymes which indicate myocardial demage. Results: In both groups, cardiac output and hemodynamic indices improved. In phenylephrine group, the systemic oxygen delivery and consumption was much higher and the myocardial oxygen extraction ratio was maintained at the lower level than the control group. In addition, the CK-MB was higher at the early phase of resuscitation and the troponin T was also higher than the control group during the whole period of resuscitation. Creatine kinase-MB increased during early resuscitation in phenylephrine group but kept decreasing after that and there's no difference between two groups. Troponin T was higher in the phenylephrine group after resuscitation. Conclusions: We concluded that phenylephrine improves myocardial oxygen balance and contractility without serious myocardial demage during resuscitation from hemorrhagic shock.

Withdrawal of vasoconstrictor influences in local metabolic coronary vasodilation

the coronary circulation has a remarkable ability to match myocardial oxygen delivery with myocardial metabolism ([3][1], [22][2]). For many years this coupling between coronary blood flow and myocardial oxygen consumption has been proposed to be primarily dependent on production of local

Effects of single-ventricle physiology with aortopulmonary shunt on regional myocardial blood flow in a piglet model

In single-ventricle physiology with aortopulmonary connection, diastolic hypotension could alter regional myocardial blood flow. Also, afterload increases could impair myocardial blood flow by increased wall tension and relative subendocardial malperfusion. This study explores the effects of acute single-ventricle physiology on regional myocardial blood flow distribution and investigates the consequences of moderate afterload augmentation on myocardial blood flow. Single-ventricle physiology was created in 8 piglets without using bypass, and 8 animals served as a sham control group. Aortopulmonary shunt, echo-guided atrial septostomy, tricuspid valve avulsion, and pulmonary artery occlusion allowed the left ventricle to support systemic and pulmonary circulations. Afterload augmentation was produced by aortic balloon inflation. Physiologic recordings and stable-isotope microsphere determination of myocardial blood flow to the subepicardium and subendocardium were obtained at baseline and during single-ventricle physiology (at 30 minutes, 120 minutes, and afterload increase). Arterial oxygen content, diastolic pressure, and coronary perfusion pressure declined after creation of single-ventricle physiology (P < .05). Acute single-ventricle physiology resulted in higher myocardial blood flow (P < .05), unchanged subendocardial/subepicardial flow ratio and oxygen delivery, and lower coronary resistance (P < .01) as compared with biventricular physiology. Afterload augmentation increased coronary perfusion pressure, causing a trend for higher myocardial blood flow and oxygen delivery (P = NS), without affecting subendocardial/subepicardial flow distribution. Myocardial oxygen supply/demand balance fell in single-ventricle physiology, remaining unchanged during afterload augmentation. Our study demonstrates that, in acute single-ventricle physiology with aortopulmonary shunt, myocardial blood flow is maintained by lower coronary perfusion pressure. Further, single-ventricle physiology results in less favorable myocardial oxygen supply/demand balance, although normal transmural myocardial blood flow distribution is maintained. Avoidance of diastolic runoff (ventricle-pulmonary conduit) could improve coronary reserve. In our study, moderate afterload augmentation did not induce relative subendocardial malperfusion, nor did it worsen oxygen supply/demand balance.

Clinical applicability of preconditioning and postconditioning: The cardiothoracic surgeons's view☆

“Any surgeon who operates upon the heart should lose the respect of his colleagues.” Theodor Billroth The field of cardiac surgery has progressed significantly since this 19th century quote from Dr Billroth. The ability to perform cardiac procedures was limited by the inability to support the circulation and to offer adequate myocardial protection. Cardiac surgery as a profession was made possible by our ability to translate experimental research into the clinical arena. Two major concepts allowed the feasibility of open-heart surgery: 1) the development of mechanical circulatory support and 2) our understanding of myocardial protection. Myocardial protection refers to all strategies that increase the myocardium's ability to withstand an ischemic insult. Ischemic and reperfusion injuries are principally responsible for cardiac failure, morbidity and mortality following cardiac surgery. Bigelow et al.'s original work on hypothermia, driven by the desire to protect the brain from ischemic insult, led to the discovery that the myocardium also benefited from hypothermia during cardiac surgery [1]. The next development in the field of myocardial protection was the use of cardioplegia. Melrose et al. first used their solution to initiate cardiac arrest as well as to cool the heart [2,3]. Their strategy combined two methods of myocardial protection: hypothermia and cardiac standstill. Both strategies reduce myocardial oxygen demand and therefore decreased ischemic injury. The field of myocardial protection then shifted to providing oxygen to the myocardium while arrested. The use of blood was introduced as a method to increase myocardial oxygen delivery [4]. Cardiac surgeons quickly adopted blood cardioplegia as their myocardial protective strategy of choice. This strategy remains the mainstay of myocardial protection. Cardioplegia protects the myocardium by providing continuous or intermittent oxygen while simultaneously reducing cardiomyocyte oxygen demand through both hypothermia and cardiac arrest. Although an effective strategy, cardioplegia does not inherently …

Part 7.4: Monitoring and Medications

This section provides an overview of monitoring techniques and medications that may be useful during CPR and in the immediate prearrest and postarrest settings. ### Assessment During CPR At present there are no reliable clinical criteria that clinicians can use to assess the efficacy of CPR. Although end-tidal CO2 serves as an indicator of cardiac output produced by chest compressions and may indicate return of spontaneous circulation (ROSC),1,2 there is little other technology available to provide real-time feedback on the effectiveness of CPR. ### Assessment of Hemodynamics #### Coronary Perfusion Pressure Coronary perfusion pressure (CPP = aortic relaxation [diastolic] pressure minus right atrial relaxation phase blood pressure) during CPR correlates with both myocardial blood flow and ROSC (LOE 3).3,4 A CPP of ≥15 mm Hg is predictive of ROSC. Increased CPP correlates with improved 24-hour survival rates in animal studies (LOE 6)5 and is associated with improved myocardial blood flow and ROSC in animal studies of epinephrine, vasopressin, and angiotensin II (LOE 6).5–7 When intra-arterial monitoring is in place during the resuscitative effort (eg, in an intensive care setting), the clinician should try to maximize arterial diastolic pressures to achieve an optimal CPP. Assuming a right atrial diastolic pressure of 10 mm Hg means that the aortic diastolic pressure should ideally be at least 30 mm Hg to maintain a CPP of ≥20 mm Hg during CPR. Unfortunately such monitoring is rarely available outside the intensive care environment. #### Pulses Clinicians frequently try to palpate arterial pulses during chest compressions to assess the effectiveness of compressions. No studies have shown the validity or clinical utility of checking pulses during ongoing CPR. Because there are no valves in the inferior vena cava, retrograde blood flow into the venous system may produce femoral vein pulsations.8 Thus palpation of a pulse in the femoral triangle may indicate venous rather than arterial …

Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo.

Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 microg.kg(-1).min(-1)); (ii) 8-Br-cGMP (50 microg.kg(-1).min(-1)); or (iii) NO synthase inhibitor L-nitro-argininemethylester (40 microg.kg(-1).min(-1); n = 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 +/- 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 +/- 13%), compared with control (167 +/- 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 +/- 7%) and 8-Br-cGMP (120 +/- 11%), compared with control (165 +/- 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and L-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors.

Normovolemic hemodilution and the heart

At the level of the heart, oxygen extraction is already nearly maximal under resting conditions. 3 Therefore, maintenance of myocardial oxygen delivery during isovolemic hemodilution depends essentially on the increase in coronary blood flow. This is achieved by a reduction in coronary vascular resistance related to the decreased blood viscosity but also to specific coronary vasodilation as demonstrated by analysis of vascular hindrance (vascular resistance/blood viscosity). 3 In addition, isovolemic hemodilution is associated with an increased cardiac work resulting in an augmentation of myocardial oxygen demand. Indeed, heart rate, 4 but also possibly myocardial contractility, 5 has been shown to increase during isovolemic hemodilution. When the hematocrit is reduced to 10 to 12%, myocardial oxygen consumption more than doubles. 6 In these conditions, coronary vasodilatation is near maximal. Below a hematocrit of 10%, coronary blood flow can no longer match the increased myocardial oxygen demand and ischemia develops, ultimately resulting in cardiac failure. This is in accordance with experimental data showing a decrease in systemic oxygen uptake at hematocrit values close to 10%. 7 As maximal coronary blood flow is not influenced by hemodilution, the coronary reserve (the ratio between maximal coronary blood flow and resting coronary blood flow) is significantly reduced during isovolemic anemia. Geha 8 demonstrated in intact dogs a 50% reduction in the coronary flow reserve when hematocrit is decreased from 43 to 20%. This indicates the vulnerability of the heart during anemia, especially if coronary artery disease (decreased maximal coronary blood flow) or higher work demands on the myocardium should co-exist. The lowest tolerable hematocrit in coronary artery disease patients is not known but experimental data in animals with extrinsically applied coronary stenosis have demonstrated a significant increase in the value of the hematocrit associated with the development of cardiac failure. 9 Based on a theoretical analysis, Kettler 10 estimated that coronary artery disease patients may tolerate some degree of hemodilution intraoperatively but will require a higher hematocrit in the early postoperative period to meet the increased tissue, and especially cardiac, oxygen demand. This has been confirmed by the study of Nelson et al., 11 showing that a postoperative hematocrit below 28% was associated with increased myocardial ischemic episodes and morbid cardiac events. Cardiovascular disease patients with a lower preoperative hematocrit have an increased risk of death when compared to non-cardiovascular disease patients with the same preoperative hematocrit. 12

Comparative Cardiac Effects of Terlipressin, Vasopressin, and Norepinephrine on an Isolated Perfused Rabbit Heart

Terlipressin, a synthetic analog of arginine-vasopressin (AVP), has been proposed as an effective vasopressive therapy in catecholamine-resistant vasodilatory shock. Although beneficial effects of terlipressin on systemic arterial pressure have been clearly demonstrated, its intrinsic effects on coronary circulation and myocardial performances remain unknown. The authors compared the coronary and myocardial effects of terlipressin (1-100 nM, n = 10), AVP (10-1000 pM, n = 10), and norepinephrine (1-100 nM, n = 10) on an erythrocyte-perfused isolated rabbit heart. The cardiac effects of terlipressin were also assessed in erythrocyte-perfused hearts in which the myocardial oxygen delivery was maintained constant and buffer-perfused hearts. Finally, the cardiac effects of terlipressin and AVP were studied in hearts pretreated by [d(CH2)5Tyr(Me)]AVP (0.1 microM), a selective V1a receptor antagonist. Norepinephrine induced a biphasic coronary effect associated with a concentration-dependent increase in myocardial performances. AVP and terlipressin significantly decreased coronary blood flow and impaired myocardial performances from 30 pM and 30 nM, respectively (P < 0.05). The cardiac side-effects of terlipressin were confirmed in buffer-perfused hearts but the maintenance of a constant myocardial oxygen delivery constant abolished its effects on myocardial performances. The cardiac effects induced by terlipressin and AVP were nearly completely abolished on hearts pretreated by [d(CH2)5Tyr(Me)]AVP. On isolated rabbit heart, terlipressin induced a coronary vasopressor effect and in turn myocardial depression only at supratherapeutic concentrations (> or =30 nM). Its effects are mainly mediated via V1a receptors. However, these potential negative side effects on the heart were less pronounced than were those of AVP.

Myocardial contractile function during post-ischemic low flow reperfusion: Critical thresholds of nicotinamide adenine dinucleotide and oxygen Delivery

Study objectives: The degree of myocardial oxygen delivery necessary to reestablish functional contractile activity after short-term global ischemia in the heart is unknown. To determine the relationship of oxygen delivery and recovery of contractile and metabolic function, we use tissue nicotinamide adenine dinucleotide (NADH) fluorometric changes to characterize adequacy of reperfusion flow. Methods: Isolated perfused rat hearts were subjected to global ischemia and reperfused at variable flow rates ranging from 1% to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. Results: A strong inverse logarithmic correlation between NADH fluorescence and reperfusion oxygen delivery (DO 2 ) was demonstrated ( r =–0.952). Left ventricle function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25% to 100% of baseline ( r =–0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% baseline DO 2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4%±3.0% mean±SEM, n=9), suggesting further reduction of the cellular redox state. This NADH increase at 1% baseline reperfusion flow was blocked by removing glucose from the perfusate. Conclusion: NADH fluorescence is a sensitive indicator of myocardial cellular oxygen use over a wide range of reperfusion DO 2 . Although oxygen is used at very low flow, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline DO 2 is necessary to restore contractile function after short-term global ischemia.

S-Nitroso Human Serum Albumin Improves Oxygen Metabolism during Reperfusion after Severe Myocardial Ischemia

Nitric oxide (NO) supplementation may modify myocardial oxygen consumption and vascular function after ischemia. We investigated the effects of the NO donor, S-nitroso human serum albumin (S-NO-HSA), on cardiac oxygen metabolism during controlled reperfusion on normothermic cardiopulmonary bypass after severe myocardial ischemia. Pigs randomly received either S-NO-HSA or human serum albumin prior to and throughout global myocardial ischemia. Myocardial oxygen utilization is impaired at the onset of reperfusion, which is not amenable to S-NO-HSA. However, NO supplementation during ongoing supply dependency of oxygen consumption eventually leads to greater myocardial oxygen delivery and consumption. In conjunction with a better washout of lactate, this indicates an improved capillary perfusion in the S-NO-HSA group during reperfusion, which results in a better contractile function post bypass.

Pulmonary edema

An acute respiratory insufficiency as a result of pulmonary oedema is regarded as a life threatening emergency event. Diagnostic classification differentiates between cardiogenic and non-cardiogenic lung oedema. Symptomatic treatment of the impaired gas exchange often precedes a causal therapy of the underlying disease. For this purpose non-invasive ventilation, in parallel with efficient medical interventions, has come into focus. Moreover, this therapeutic intervention can prevent from the necessity of endotracheal intubation in the majority of cases. Rapid restoration of arterial oxygenation along with medical support of the cardiac function (i.e. by nitrates, diuretics, ACE-inhibitors, etc.) results in improved myocardial oxygen-delivery and reduced oxygen-consumption. This article reviews mainly the pathophysiology of cardiogenic lung edema, while most of the currently discussed therapeutic implications also apply to other entities of lung edema.

Myocardial contractile function during postischemic low-flow reperfusion: critical thresholds of NADH and O2 delivery.

The degree of myocardial oxygen delivery (Do2) that is necessary to reestablish functional contractile activity after short-term global ischemia in heart is not known. To determine the relationship between Do2 and recovery of contractile and metabolic functions, we used tissue NADH fluorometric changes to characterize adequacy of reperfusion flow. Isolated perfused rat hearts were subjected to global ischemia and were reperfused at variable flow rates that ranged from 1 to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. A strong inverse logarithmic correlation between NADH fluorescence and reperfusion Do2 was demonstrated (r = -0.952). Left ventricular function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25 to 100% of baseline (r = -0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% of baseline Do2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4 +/- 3.0%, means +/- SE, n = 9), which suggests further reduction of the cellular redox state. This NADH increase at 1% of baseline reperfusion flow was blocked by removing glucose from the perfusate. NADH fluorescence is a sensitive indicator of myocardial cellular oxygen utilization over a wide range of reperfusion Do2 values. Although oxygen is utilized at very low flow rates, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline Do2 is necessary to restore contractile function after short-term global ischemia.

Coronary blood flow regulation in the prediabetic metabolic syndrome

This study tested whether the pre-diabetic metabolic syndrome impairs coronary blood flow control sufficiently to alter the balance between coronary blood flow and myocardial metabolism. Experiments were conducted in dogs instrumented with catheters in the aorta, coronary sinus, and left ventricle and with flow transducers around the circumflex coronary artery and aorta. Coronary blood flow, myocardial oxygen consumption (MVO(2)), cardiac output, aortic pressure, left ventricular pressure and heart rate were measured at rest and during treadmill exercise in normal, control and high fat fed dogs. High fat feeding for approximately six weeks increased body weight 15%, increased aortic blood pressure 10%, and induced insulin resistance. Fasting plasma insulin levels were increased 2.4-fold while plasma glucose concentration was unchanged relative to controls (5.0 +/- 0.3 mM). The cardiac index increased with exercise but was not altered by high fat feeding. The metabolic syndrome reduced the slope of the relationship between coronary blood flow and MVO(2) ( P < 0.0001) and decreased coronary venous PO(2) at a given level of MVO(2) ( P < 0.05). These findings indicate that the metabolic syndrome impairs the balance between myocardial oxygen delivery and metabolism by tonically vasoconstricting the coronary circulation.

Coronary blood flow control is impaired at rest and during exercise in conscious diabetic dogs.

This study tested whether diabetes mellitus impairs coronary blood flow control sufficiently to alter the balance between myocardial oxygen delivery and metabolism. Dogs (n = 7) were instrumented with catheters in the aorta and coronary sinus, and with a flow transducer on the circumflex coronary artery. Coronary blood flow, myocardial oxygen consumption (MVO2), heart rate and aortic pressure were measured at rest and during treadmill exercise before and after induction of diabetes with alloxan monohydrate (40 - 60 mg/kg). Arterial plasma glucose concentration increased from 4.6+/-0.2 mM in non-diabetic, control dogs to 20.2+/-2.3 mM one week after alloxan injection. In non-diabetic control dogs, exercise increased MVO2 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.4-fold. Coronary venous PO2 decreased from 19.4+/-0.6 mmHg at rest to 14.7+/-0.7 mmHg during exercise. Diabetes significantly attenuated exercise coronary hyperemia and reduced coronary venous PO2 at rest (15.6+/-0.5 mmHg) and during exercise (12.6+/-0.8 mmHg). Diabetes also significantly reduced myocardial oxygen delivery at each level of exercise. Acute hyperglycemia alone did not alter exercise-induced coronary vasodilation or reduce coronary venous PO2. These findings demonstrate that experimental diabetes attenuates functional coronary hyperemia and impairs the balance between coronary blood flow and myocardial metabolism. However, this deleterious effect is not related to acute hyperglycemia but to the chronic disease process of diabetes mellitus.

Dynamic changes in three-dimensional architecture and vascular volume of transmural coronary microvasculature between diastolic- and systolic-arrested rat hearts.

The phase difference of coronary arterial and venous flows indicates the importance of intramyocardial capacitance vessels in storing diastolic flow and in discharging volume in systole. However, the anatomic and functional characteristics of the capacitance vessels are unclear. We aimed to clarify those characteristics with their transmural difference by 3D visualization of transmural microvessels under diastole and systole. We performed complete intracoronary filling of a contrast medium into Langendorff's Wistar rat hearts under (1) St Thomas-perfused diastolic arrest (D-mode) and (2) BaCl(2)-induced systolic arrest (S-mode). Precise transmural 3D architectures of capillaries and of pre- and post-capillary microvessels (ie, microvessels larger than capillaries) were visualized clearly with a confocal laser scanning microscope and x-ray microcomputed tomography (microCT), respectively. Vascular volume fraction (VF) and systolic-induced VF reduction rate from D- to S-mode were analyzed. The net capillary VF in D-mode (20.4 +/- 0.9%) was 10 times that of larger microvessels and was reduced in S-mode by 32% without capillary collapse. Systolic-induced VF reduction rate was smaller in capillaries than in larger microvessels (48%; P<0.05). The larger microvessel VF in D-mode (2.2 +/-0.2%) was reduced in S-mode, accompanied by complicated 3D deformation. Capillaries were relatively resistant to the systolic extravascular compression compared with pre- and post-capillary microvessels, conveniently beneficial for the myocardial oxygen delivery throughout a cardiac cycle. Nevertheless, a larger change in the absolute volume of capillaries may function as effective capacitance. On one hand, the pre- and post-capillary microvessels showed a larger phasic change in resistance, which may function to maintain the capillary patency during systole.

Preserved myocardial blood flow and oxygen supply-demand balance with active coronary perfusion during simulated off-pump coronary artery bypass grafting.

During off-pump coronary artery bypass surgery, concern remains about the possible myocardial injury associated with the transient occlusion and stabilization of the target vessels. Although intraluminal shunts are used to avoid ischemia during graft anastomosis, blood flow through the shunts can be affected by upstream pressure and inherent resistance, resulting in reduced blood flow during hypotension or severe proximal stenosis. In anesthetized dogs regional myocardial blood flow (microspheres), oxygen consumption, lactate extraction, and systolic shortening (sonomicrometry) were measured in the myocardium served by the left anterior descending coronary artery with native perfusion after interposition of a 2.25-mm shunt (> or = 90% of left anterior descending diameter) and during active coronary perfusion with a constant flow pump. Measurements were made under normotension and hypotension produced by partial caval occlusion to reduce arterial pressure by 50%. Interposition of the shunt reduced blood flow by 67.8%, regional oxygen delivery by 59.8%, and systolic shortening by 45.6% relative to baseline, but lactate extraction (31.0% vs 31.2%) and oxygen supply-consumption (O(2)S/myocardial oxygen consumption ratio, 2.7 +/- 0.5 vs 2.6 +/- 0.5) were comparable with baseline values. Hypotension further decreased these physiologic values and was associated with local lactate production (-67.4% extraction) and decreased O(2)S/myocardial oxygen consumption ratio (1.3 +/- 0.1). Active coronary perfusion was associated with regional blood flow, oxygen delivery, systolic shortening, and lactate extraction comparable with baseline values. In contrast to the shunt, active perfusion maintained myocardial flow, oxygen delivery, and lactate extraction during hypotension and normalized the O(2)S/myocardial oxygen consumption ratio, although systolic shortening decreased as a result of ventricular unloading. Intraluminal shunts may impede oxygen delivery to the target myocardium, which precipitates regional ischemia during transient hypotension. Active coronary perfusion provides adequate oxygen supply independent of systemic blood pressure.