Dihydroergotoxine,an ergot alkaloid without marked hypotensive effect,improves blood flow and metabolism in the underperfused canine myocardium

Summary Regional myocardial blood flow was assessed in 6 anaesthetized dogs using radiolabelled microspheres. Lactate, H⁺, and O₂ content were measured in arterial and local venous blood, obtained from the area supplied by the circumflex branch of the left coronary artery (LCX). Constriction of LCX by 67% led to considerable hemodynamic changes indicative of depressed global myocardial function. A significant release of lactate from the underperfused part of the left ventricle was recorded. Infusion of 0.7 g/kg dihydroergotoxine over a period of 5 min induced a decrease in heart rate, left ventricular dp/dt max, and cardiac output, a sustained increase in total peripheral and femoral resistance and a transient increase in mean arterial blood pressure. Dihydroergotoxine markedly reduced lactate release and even, in some cases, induced lactate uptake and led to a significant increase in the endocardial blood flow both in the underperfused and normally perfused left ventricle.It is concluded that dihydroergotoxine, due to its ability to reduce myocardial oxygen demand and owing to its -sympatholytic activity, which is not accompanied by any marked decrease in arterial blood pressure, causes improvement in blood flow in the underperfused myocardium and a marked amelioration of the impaired metabolic processes.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung.     

Effects of the NO donor sodium nitroprusside on oxygen consumption and energetics in rabbit myocardium

Nitric oxide (NO) has influence on various cellular functions. Little is known of the influence of NO on myocardial energetics. In the present study oxygen consumption and mechanical parameters of isometrically contracting rabbit papillary muscles (1 Hz stimulation frequency) were investigated at varying interventions while maintaining physiological conditions (37°C; 2.5 mM Ca²⁺) to study the effects of NO on energetics. The NO donor sodium nitroprusside (SNP) showed a negative inotropic effect. SNP decreased the maximal force in normal rabbit muscle strips by 30%, the force time integral (FTI) by 40% and the relaxation time by 20%. In addition the oxygen consumption decreased by 60%, a notably disproportional decrease compared to the mechanical parameters. Consequently, the economy as a ratio of FTI and oxygen consumption is significantly increased by SNP. In contrast the negative inotropic effect due to a reduction in extracellular Calcium (Ca²⁺) from 2.5 to 1.25 mM reduced FTI and oxygen consumption proportionally by 40% and did not change economy. The effect of NO on force and oxygen consumption could be reproduced by the application of the cyclic guanosine monophosphate (cGMP) analogue 8-bromo-cGMP. In summary, NO increased the economy of isometrically contracting papillary muscles. The improvement in contraction economy under NO seems to be mediated by cGMP as the secondary messenger and maybe due to alterations of the crossbridge cycle. Returned for 1. Revision: 25 April 2008 1. Revision received: 8 August 2008 Returned for 2. Revision: 25 August 2008. 2. Revision received: 15 December 2008     

Oxidative metabolism and myocardial blood flow changes after transthoracic DC countershocks in dogs.

Changes in oxidative metabolism and myocardial blood flow were investigated in adult greyhounds following transthoracic shocks from a DC cardiac defibrillator (400 Joules stored energy, damped sine wave, 0.5 min intervals). Myocardial lactate extraction became negative maximally at 1 min, following both two (mean -24% +/- SEM24) or five (-193% +/- 148) shocks and returned to baseline by 6-15 min. Transient reductions were also observed in myocardial extraction of pyruvate and free fatty acids but not glucose. Myocardial necrosis assessed at 4 h following the shocks was 0.05 g (+/- 0.03) after two shocks, 6.5 g (+/- 1.5) after five shocks and zero in controls. Mean peak noradrenaline levels in arterial (785 +/- 319 pg.ml-1) and coronary sinus (916 +/- 313 pg.ml-1) blood at 1 min after five shocks were higher than after 0 shocks (82 +/- 33 pg.ml-1 and 201 +/- 63 pg.ml-1 respectively), P < 0.05. Great cardiac venous blood flow was measured by a thermodilution technique, with continuous infusion of 0.9% saline, before, during and after five shocks. Mean blood flow fell from 47 +/- 13 ml.min-1 to a minimum of 36 +/- 7 ml.min-1 during shocks, and then rose to 83 +/- 17 ml.min-1 at 2 min after the fifth shock (P < 0.05). Following damaging countershocks, oxidative metabolism is depressed, in keeping with a primary disturbance of mitochondrial function. These metabolic changes are not secondary to ischaemia, since an increase in blood flow in the great cardiac vein (GCV) is observed. Vasodilatation of the coronary vascular bed must occur to account for this.     

Effects of coronary revascularisation on myocardial blood flow and coronary vasodilator reserve in hibernating myocardium

OBJECTIVE—Previous studies have suggested that resting myocardial blood flow is within normal limits in most chronically dysfunctional left ventricular segments which improve function after coronary artery revascularisation (hibernating myocardium). The aim of this study was to assess myocardial blood flow and coronary vasodilator reserve in hibernating myocardium before and after coronary revascularisation.
PATIENTS AND METHODS— 30 patients with multivessel coronary disease undergoing coronary revascularisation (21 patients with bypass grafting and nine with coronary angioplasty), and 21 age and sex matched healthy volunteers (controls). Myocardial blood flow (MBF, ml/min/g) was measured by positron emission tomography using oxygen-15 water at rest and after dipyridamole (MBFdip, 0.56 mg/kg in four minutes). Coronary vasodilator reserve was calculated as MBFdip/MBF. Regional wall motion was assessed with echocardiography.
RESULTS—Before revascularisation there were 48 remote and 275 dysfunctional myocardial segments, of which 163 (59%) improved function after revascularisation (hibernating). In hibernating segments coronary vasodilator reserve before revascularisation was significantly lower than in remote segments (1.97 (0.7), p < 0.0001) and controls (3.2 (1.5), p < 0.0001). In hibernating segments, myocardial blood flow remained unchanged after revascularisation (0.94 (0.3) v 0.95 (0.3) ml/min/g, p = 0.3) while coronary vasodilator reserve increased (1.47 (0.7) v 1.98 (1.0), p < 0.0001). Myocardial blood flow was similar in remote, hibernating segments before and after revascularisation and in controls.
CONCLUSIONS—This study confirms that myocardial blood flow at rest in hibernating myocardium is within normal limits in most segments, and that hibernating myocardium is characterised by an impaired coronary vasodilator reserve which improves significantly after coronary revascularisation.


Keywords: hibernating myocardium; myocardial blood flow; heart failure; positron emission tomography     

Blood flow distribution in the left ventricular free wall in open-chest dogs

Summary The distribution of blood flow in various layers of the normally perfused left ventricular free wall was studied in open-chest dogs, using 15-m radioactive microspheres. The most pronounced variations were found in epicardial blood flow, which was higher near the apex than near the base and lower along the marginal branch of the left circumflex coronary artery than along the left interventricular coronary artery. The variations in endocardial blood flow were less pronounced, while blood flow in the middle layers was about equally distributed. Consequently the endo/epicardial blood flow ratios, varied over the left ventricular free wall. Possible causes of the inhomogeneities in blood flow distribution are discussed.The investigation was (partly) supported by the Foundation for Medical Research FUNGO, which is subsidized by the Netherlands Organization for the Advancement of Pure Research (ZWO).     

Effects of coronary occlusion and norepinephrine on the myocardium of alloxan-diabetic dogs

Summary The aim of this study was to clarify the role of altered diabetic vascular reactivity in ischaemic heart disease. In diabetic condition, the necrotic area of myocardial infarction was significantly extended and myocardial oedema failed to develop after administration of norepinephrine 2 or 48 hours after ligation of the left anterior descending coronary artery. In metabolically healthy dogs the necrotic area of myocardial infarction was considerably smaller and an increase in myocardial water content, in myocardial thiocyanate space, in microscopically demonstrable permeability and in diastolic stiffness of left ventricular wall occurred when norepinephrine was administered 2 or 48 hours after coronary infarction. A close correlation was demonstrable between enhanced water content, thiocyanate space and diastolic stiffness in metabolically healthy animals, whereas in diabetic condition diastolic stiffness was primarily increased, and decreased when norepinephrine was infused after coronary ligation. Therefore, the altered vascular reactivity in diabetes is supposed to be responsible for the lack of oedema in the nonischaemic part of myocardium after norepinephrine infusion as well as for the size and severity of myocardial infarction.

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Zusammenfassung Es wurde bewiesen, daß die Verabreichung von Noradrenalin 2 und 48 Stunden nach Okklusion der vorderen, absteigenden Koronararterie eine Erhöhung des Wassergehaltes, des Thiocyanat-Raumes, der mikroskopisch nachweisbaren Permeabilität sowie der diastolischen Steifheit in dem nichtischämischen Teil der linken Herzkammerwand hervorruft. Bei diabetischen Tieren war das ischämische Areal wesentlich größer, und es trat kein Myokardödem auf. Bei stoffwechselgesunden Tieren konnte eine strenge Korrelation zwischen den erhöhten Werten des Wassergehalts, des Thiocyanat-Raumes sowie der diastolischen Steifheit dargestellt werden. In diabetischen Tieren war dagegen die diastolische Steifheit von vornherein erhöht und nahm ab, wenn nach der Koronarunterbindung Noradrenalin infundiert wurde. Deshalb wird angenommen, daß die veränderte Gefäßreaktivität bei Diabetes sowohl für das Ausbleiben eines Ödems im nichtischämischen Anteil des Myokards nach Noradrenalin-Infusion verantwortlich ist als auch für Ausmaß und Schweregrad des Myokardinfarktes.

     

多巴酚丁胺对冬眠心肌灌注,代谢及功能的影响及其临床意义

目的 探讨多巴酚丁胺负荷试验（ＤＳＴ）对冬眠心肌灌注、代谢和功能的影响及其临床意义。方法 结扎猪冠状动脉左前降支制作心肌冬眠模型。２０只猪在冠状动脉结扎前的非缺血阶段作用对照组。然后按缺血程度分成中度和重度缺血的心肌冬眠分别为甲组和乙组,每组各１０只。采用ＤＳＴ“唤醒冬眠心肌,测量各试验阶段心肌灌注（ＭＢＦ）、代谢（ＭＶＯ２、ＱＬａｃ、ｐＨｖ）、收缩功能（ＷＴ）及血流动力学（ＲＰＰ）指标,比较组仙     

Cardiac tamponade in dogs with normal coronary arteries. II. Myocardial flow and metabolism with moderate and severe hemodynamic impairment

Summary To determine the effects of cardiac tamponade on myocardial blood flow and its distribution, dogs were prepared with indwelling pericardial catheters. Hemodynamic, myocardial blood flow, and myocardial metabolic data were collected in 5 closed-chest, spontaneously breathing animals with normal blood volumes and hemoglobin concentrations and 6 with acute anemia. Instillation of an average of 89.0±14.9 ml of modified Normosol® into the pericardial space in dogs with normal hemoglobin levels produced mild tamponade with a modest decline in aortic pressure (119.5±14.3 to 96.8±12.1 mm Hg) and significant rises in left and right atrial and pericardial pressures to 7–8 mm Hg. Increasing the pericardial volume to 124.0±13.6 ml produced hypotension (mean aortic pressure 86.2±10.5 mm Hg) and rises in the left and right ventricular filling pressures and pericardial pressure to 10–11 mm Hg. Total myocardial blood flow fell from 1.19±0.18 to 0.73±0.17 ml/min/g (p<0.02) during mild tamponade, and fell further to 0.56±0.17 ml/min/g (p<0.05) with more severe tamponade. Despite these declines, the left ventricular wall inner/outer flow ratio and left ventricular flow as a proportion of total cardiac output were unchanged. In dogs with anemia more severe tamponade was created, with consequently more marked hemodynamic abnormalities. However, the relative changes in myocardial blood flow and inner/outer flow ratio were similar. Myocardial metabolic parameters could be evaluated only in the dogs with less severe tamponade. The coronary arteriovenous oxygen difference changed little during induced tamponade, and, therefore, quantitated myocardial oxygen consumption declined in proportion to the fall in myocardial flow. Furthermore, myocardial lactate extraction and the lactate/pyruvate ratio were not affected by cardiac tamponade. Thus, these experiments cannot support the hypothesis that myocardial ischemia is a pathophysiologic factor in the production of abnormal hemodynamics in cardiac tamponade.Dr. Cohen is the recipient of a Research Career Development Award from the National Heart, Lung and Blood Institute Grant HL-00281.This study was supported in part by National Heart, Lung and Blood Institute Grant HL-17809.     

Effects of C-peptide on blood flow,capillary diffusion capacity and glucose utilization in the exercising forearm of Type 1 (insulin-dependent) diabetic patients

Summary Microvascular dysfunction is frequently seen in patients with Type 1 (insulin-dependent) diabetes. The present study was undertaken to examine whether skeletal muscle microcirculation in Type 1 diabetic patients is influenced by C-peptide. Forearm blood flow, capillary diffusion capacity and substrate exchange were studied during strenuous rhythmic forearm exercise on a hand ergometer. Measurements were made before and during i.v. infusion for 60 min of C-peptide or 0.9% NaCl in Type 1 diabetic patients and healthy subjects. During infusion the C-peptide levels in the diabetic patients increased from less than 0.05 nmol/l to 1.32±0.08 nmol/l. Prior to infusion forearm blood flow and capillary diffusion capacity during exercise were lower in the diabetic patients than the control subjects. During C-peptide infusion both variables increased in the diabetic patients (blood flow +27±4%, capillary diffusion capacity +52±9%) to levels similar to those in the healthy subjects, while no significant change was seen in the healthy control subjects or the diabetic patients given NaCl. Forearm uptake of oxygen and glucose in the diabetic patients increased markedly after C-peptide administration but were unchanged after NaCl infusion. Significant uptake of C-peptide to the deep forearm tissues was observed in the resting state; approximately 7±2% of the arterial C-peptide concentration was extracted by forearm tissues in diabetic patients as well as in healthy control subjects. It is concluded that replacement of C-peptide to physiological levels in young Type 1 diabetic patients results in a normalization of both blood flow and capillary diffusion capacity during exercise, as well as augmented uptake of oxygen and glucose by exercising muscle. The findings suggest that C-peptide may be of importance for microvascular function in exercising muscle in Type 1 diabetes. Finally, skeletal muscle is a major site of C-peptide disposal.     

Regional asynchrony of segmental contraction may explain the “oxygen consumption paradox” in stunned myocardium

Summary Despite apparently depressed function, stunned myocardium maintains oxygen consumption and has the capacity to increase contractility with inotropic stimulation. We hypothesized that during stunning, O₂ demand is maintained because regional segment work is performed, but is asynchronous with global left ventricular contraction, and that inotropic stimulation would restore regional work and synchrony. Thirteen open-chest anesthetized dogs were subjected to three left anterior descending (LAD) coronary artery occlusions (10 min) and reperfusions (15 min) to produce regional myocardial stunning. Segment shortening and force development were measured independently and simultaneously in the LAD (experimental) region and circumflex (control) regions. Regional myocardial work was calculated as the integrated product of instantaneous force and shortening, during two periods: 1) over the entire cardiac cycle (Positive Work), and 2) limited to the systolic portion of the cardiac cycle (Systolic Work). Regional myocardial O₂ consumption (MVO₂) was calculated from regional blood flow (radiolabeled microspheres) and O₂ saturation data (microspectrophotometry). Occlusion of the LAD produced a delay in onset of segment shortening in the ischemic region, but not in regional force development. A time delay of 67–81 ms persisted through the three stages of occlusions and reperfusion. Systolic regional work was depressed to a greater extent (924±182 to 149±118 g*mm*min^–1) than total positive regional work (1437±337 to 857±174 g*mm*min^–1). Regional subepicardial MVO₂ in the stunned region was not different than in the control region (7.3±1.5 vs. 6.9±1.4 ml O₂*min^–1*100 g^–1). Local infusion of isoproterenol reversed the delay in regional shortening from 73±7 to 21±8 ms, thereby augmenting systolic work (298%) more than positive work (60%), without a significant increase in MVO₂ (7.3±1.5 to 10.5±3.2 ml O₂*min^–1*100 g^–1). It is concluded that myocardial stunning decreases regional systolic work due to regional mechanical asynchrony, while MVO₂ is used supported total positive work which was not significantly reduced. Isoproterenol restores regional work by restoring synchrony, without greatly affecting regional MVO₂.This study was supported in part by a research grant from the Schulz Foundation and USPHS grant HL40320.     

Evidence of anaerobic metabolism during low-level exercise testing in high-risk postmyocardial infarction patients

Low-level exercise testing was performed on 31 patients 7.4 +/- 2.7 days following an acute myocardial infarction. Measurements of oxygen consumption (VO2) and arterial serum lactate were made at rest and during exercise in these patients and 15 normal subjects. The patients were subdivided into finishers (F) and nonfinishers (NF) of the low-level protocol. The NF group had 2.5 +/- 6 stenosed vessels and an ejection fraction of 44 +/- 11% compared to F subjects, who had 1.4 +/- 1 vessels stenosed (p less than .001) and an ejection fraction of 54 +/- 14% (p less than .05). Finishers had significantly higher VO2 than the nonfinishers (14.5 +/- 2.5 ml/kg/min vs. 11.2 +/- 3.5 ml/kg/min p less than .01). At the end of exercise serum lactate level was 1.18 +/- .59 mM in normals, 1.43 +/- .52 mM in finishers, and 2.15 +/- .9 mM in nonfinishers. The change in serum lactate from rest to end exercise divided by the change in VO2 from rest to end exercise was .039 +/- .038 mM/ml kg per min in normals, .075 +/- .045 mM/ml kg per min in finishers (p less than .03 vs. normal), and .210 +/- .189 mM/ml kg per min for nonfinishers (p less than .001 vs. normal). These results indicate that nonfinishers produce more lactate and use less oxygen during low-level exercise, suggesting that working muscles are deriving energy by anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)     

养阴通脑颗粒对麻醉犬脑血流量的影响

目的 :观察养阴通脑颗粒对麻醉犬脑血流量的影响。方法 :将 2 9只犬随机分为 5组 ,养阴通脑颗粒大剂量组（2 .0 g/kg） ;中剂量组 （1.0 g/kg） ;小剂量组 （0 .5 g/kg）及阳性药维脑路通组 （维脑路通 0 .0 2 5 g/kg） ,空白对照组给等量的生理盐水。结果 :养阴通脑颗粒 （0 .5 ,1.0 ,2 .0 g/kg）可增加麻醉犬的脑血流量 ,中剂量组在 30～ 90 m in时增加更明显 ,与维脑路通组比较 ,在 30 min时 ,大、中剂量组的脑血流量比维脑路通组明显 （P<0 .0 5 ）。结论 :养阴通脑颗粒扩张脑血管的疗效比小剂量的维脑路通好。     

曲美他嗪对心肌缺血时细胞骨架损伤的作用

目的　探讨心肌缺血时细胞骨架改变并观察曲美他嗪对心肌缺血时细胞骨架损伤的影响 ,为临床应用提供理论依据。方法　将大白鼠随机分为对照组和用药组并制成缺血模型 ,分别于缺血 30 m in、6 0 min、12 0 min时取心肌组织用免疫组化的方法观察肌动蛋白、波形蛋白、肌球蛋白、结蛋白等心肌细胞骨架蛋白的改变 ,并用计算机图象模拟分析系统计算骨架蛋白量的变化。结果　心肌缺血 30 min即有肌动蛋白、肌球蛋白损伤 ,12 0 min时有结蛋白损伤 (P<0 .0 5 )。曲美他嗪干预后 ,心肌缺血 6 0 min、12 0 min时肌动蛋白、肌球蛋白损伤明显减少 (P<0 .0 5 )。结论　心肌缺血时可以导致细胞骨架损伤 ,曲美他嗪对心肌缺血时细胞骨架损伤有保护作用     

Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin

Abstract: 10 subjects with Hb Linkdping (β 36 Pro>Thr), a high-affinity hemoglobin variant, with a P₅₀ of 2.2 kPa (16.5 mm Hg) were investigated before and 3–4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 ± 13 (SD) to 146 ± 15 g 1^-1and the red cell volume from 2.77 ± 0.83 to 2.23 ± 0.67 1. Maximal oxygen consumption decreased slightly by 2.7 ± 3.8 ml min^-1kg^-1and maximal exercise power by 11 ± 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (— 1.1 ± 6.4 beats min^-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 ± 10.3 ml min^-1100 g^-1from before to after hemodilution. The results indicate that subjects with Hb Linkoping have only limited benefit from their increased blood hemoglobin concentration.     

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. Received: 19 July 2001, Returned for 1. revision: 20 August 2001, 1. Revision received: 17 October 2001, Returned for 2. revision: 19 October 2001, 2. Revision received: 2 November 2001, Accepted: 5 November 2001     

Effects of the carbonic anhydrase inhibitor acetazolamide on splanchnic blood flow in anaesthetized rats

The aim of the present study was to evaluate whether inhibition of the enzyme carbonic anhydrase with acetazolamide interfered with pancreatic islet and whole splanchnic blood perfusion in rats. Carbonic anhydrase is present both in the endocrine cells and, in particular, the endothelium of the pancreatic islet. Thiobutabarbital-anaesthetized, male Sprague-Dawley rats were used in all experiments, and acetazolamide (50 mg/kg body weight) was given to untreated control rats or rats pretreated with glucose, i.e. to normoglycaemic and hyperglycaemic animals. No acetazolamide-induced effects on blood glucose or serum insulin concentrations, mean arterial blood pressure, whole pancreatic or islet blood flow were seen in any of the animals. There were no effects on duodenal or colonic blood flow recorded in the control rats, whereas an increase in duodenal blood flow (P<0.02) was observed in the hyperglycaemic animals. A tendency to an increase was seen in colonic blood flow in hyperglycaemic animals, although this was not statistically significant (P=0.069). Inhibition of carbonic anhydrase seems to induce only minor effects on pancreatic blood flow, while duodenal blood flow is slightly enhanced in hyperglycaemic animals. Received: 25 May 1998 / Accepted in revised form: 23 October 1998     

Nonlinear coupling between cerebral blood flow,oxygen consumption,and ATP production in human visual cortex

The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production (J_ATP)] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO₂; i.e., index of aerobic metabolism), and lactate production (J_Lac; i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in J_ATP were small (12.2–16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %ΔJ_ATP being linearly correlated with the percentage change in CMRO₂ (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7–65.1%) and negatively correlated with the percentage change in CMRO₂ (r = −0.64, P = 0.024), but positively correlated with %ΔJ_Lac (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand.     

Effects of glucose-insulin-potassium (GIK) on myocardial blood flow and metabolism in canine endotoxin shock

Glucose-insulin-potassium (GIK) has beneficial effects during endotoxin shock, possibly through improvement of myocardial function, but the mechanism is not clear. We have studied the effects of GIK on left ventricular function, coronary flow, and oxygen consumption in controls and dogs treated with endotoxin (1.5 mg/kg-1). The animals were anaesthetized (etomidate 4 mg/kg-1/hr-1) and ventilated (N2O:O2 = 2:1). We have measured left ventricular pressure, left ventricular end-diastolic pressure (LVEDP) and LVdP/dt, systemic blood pressure, cardiac output (CO; thermodilution), coronary blood flow (CBF; radioactive microspheres), and oxygen content and lactate in arterial and coronary sinus blood. Endotoxin caused a rapid fall of CO and blood pressure with a temporary recovery followed by gradual circulatory collapse. GIK infusion (50% glucose, 2 g/kg-1 bw, 8 mmol KCl, and 3 U insulin/kg-1 bw) increased CO (56%), CBF (61%), blood pressure (21%), LVEDP (77%), and LVdP/dt (28%), and systemic vascular resistance decreased (23%). Stroke work (80%) and tension time index (42%) decreased during shock, but GIK temporarily improved these variables. The ratio of stroke work, respectively tension time index to oxygen consumption, suggests that myocardial efficiency decreased during shock and improved after GIK. Endotoxin decreased the ratio of endo- to epicardial flow. GIK did not change this ratio. However, for the same endo to epi ratio, increased CBF implies increased flow to endocardium.     

Effects of prostacyclin (PGI2) and adenosine (ASN) on total and regional blood flow of isolated,collateralized dog hearts

Summary Dogs were subjected to chronic occlusion of the left circumflex and the right coronary artery by ameroid-type constrictors 4–5 weeks before the experiments. The hearts were isolated, fibrillated and perfused with blood (100 mmHg) from a support dog. Total and regional myocardial blood flow as well as peripheral coronary pressure (circumflex artery) were determined before and during infusion of PGI₂ and ASN into the isolated hearts. Both drugs increased total and regional blood flow to all parts of the myocardium in a dose-dependent manner, PGI₂ being 2–3 times more potent than ASN. The perfusion pressure for the collateral-dependent myocardium, the peripheral coronary pressure, decreased following high doses of both drugs. For PGI₂ a dose level existed where total flow was increased, while peripheral coronary pressure remained unaffected. After termination of the infusion of PGI₂, peripheral coronary pressure rose above predrug level with the total blood flow still being elevated. These findings indicate a PGI₂-induced dilatation of collateral vessels. In general, the hemodynamic profile within the isolated hearts and the support dogs was characterized by the pronounced vasodilatory effects of PGI₂ on arterioles. However, these effects did not deteriorate further the nonhomogenous blood flow distribution in the collateralized portions of the myocardium.The findings suggest that PGI₂ is not a specific coronary vasodilator.