Residual Blood Flow Research Articles

Diabetes insipidus accompanying brain death in children.

Diabetes insipidus (DI) developed in 14 of 16 children who satisfied criteria for brain death. The occurrence of DI after an hypoxic/ischemic insult may represent midbrain death and seems to be a clinically useful sign in the diagnosis of brain death in children. In two patients, DI resolved spontaneously; these patients and children without DI may have had small areas of residual cerebral blood flow and brain function. The onset or cessation of DI was temporally associated with the use of dopamine in three patients.

Usefulness of intravenous propranolol in predicting left anterior descending blood flow during anterior myocardial infarction

The effect of propranolol on precordial ST-segment elevation was studied in 24 patients with acute anterior myocardial infarction. The electrocardiographic response to the drug was correlated with the early angiographic appearance of the left anterior descending coronary artery (LAD). After a 30-minute observation period, intravenous propranolol (average dose 3.5 ± 2.2 mg) was given a mean of 2.8 ± 1.9 hours after the onset of persistent chest pain. Coronary angiography was performed 3.6 ± 2.0 hours after the onset of symptoms. Patients were classified into 2 groups according to the angiographic findings. Group A consisted of 7 patients with a stenotic but patent LAD and 1 patiënt with excellent collateral blood flow to that area. Group B consisted of 16 patients with a completely occluded LAD and poor or absent collateral blood flow. Patients in group A showed a mean reduction in precordial ST-segment elevation of 77 ± 18% and patients in group B showed a mean reduction of 13 ± 14% (p < 0.005). Left ventricular ejection fraction at discharge was 0.6 ± 0.07 in group A and 0.37 ± 0.08 in group B (p < 0.001). Thus, the electrocardiographic response to intravenous propranolol given early in the course of acute anterior myocardial infarction predicts the presence of blood flow to the infarcting zone. The combination of residual blood flow and reduction of ST-segment elevation secondary to propranolol is associated with preservation of ventricular function.

Persistence of auditory nerve response and absence of brain-stem response in severe cerebral ischaemia

Cerebral ischaemia, in which the brain-stem components of the ABP were isoelectric, was accompanied by the paradoxical persistence of the compound action potential of the auditory nerve (wave 1). This ischaemia was induced in cats by reducing mean arterial blood pressure and elevating intracranial pressure, resulting in decreased cerebral perfusion pressure (CPP). This is unexpected since the inner ear is supplied by a branch of an intracranial artery. To study this phenomenon, CPP was manipulated and when average CPP was 13.5 mm Hg, only wave 1 remained. In 7 of 9 experiments, clamping of both common carotid arteries did not abolish wave 1. Experiments with radioactive tracers demonstrated a remaining residual blood flow through the inner ear. This remaining auditory nerve response is probably not due to a very low metabolism of the inner ear or to the cochlea being supplied by anastosomes from the middle ear, supplied by the external carotid artery. The residual cochlear blood flow and the persistent wave 1 can probably be explained in the following way at low CPPs the smaller intracranial blood vessels collapse so that the brain tissue is not perfused, leading to loss of the brain-stem components of the ABP. However, flow still persists in the larger intracranial arteries. This blood preferentially flows to the cochlea since the intracochlear pressure is slightly below the intracranial pressure due to the presence of the oval and round windows. Thus a sufficient blood flow to the cochlea is maintained, with sparing of wave 1.

Experimental studies into mechanisms of cardiac arrest.

Experimental studies have revealed that a wide variety of different pathophysiological mechanisms may induce ventricular fibrillation (VF) and cardiac arrest during acute myocardial ischaemia or infarction. Distinct phases of enhanced vulnerability (the amount of current required to stimulate ectopic activity in the heart following application of an extra stimulus) to VF follow coronary occlusion and correspond to 'pre-hospital', 'in-hospital' and 'out-of-hospital' periods of arrhythmogenesis. Electrophysiological evidence suggests very early (phase 1a) VF results from multiple re-entrant excitation within the ischaemic zone. Slowed and fragmented conduction and inhomogeneities in refractoriness rapidly develop which mapping studies show to occur in association with development of spatial inhomogeneities in residual blood flow distribution and metabolism. Onset of VF may be triggered by adrenergic mechanisms or influenced by peripheral metabolic responses. Automatic mechanisms (spontaneous pacemaker activity) may induce later VF or VF on reperfusion or trigger re-entry. Findings indicate no single therapeutic approach to be likely to protect against all forms of cardiac arrest.

Distribution of the collateral blood flow at the lateral border of the ischemic myocardium after acute coronary occlusion in the pig and the dog.

Residual blood flow in pigs (n = 8) and dogs (n = 11) was measured by tracer microspheres (85Sr) 1 hour after occlusion of the left anterior descending coronary artery (LAD). Collateral blood flow was distinguished from overlap flow, defined as the blood flow of non-ischemic myocardium interdigitating into the ischemic area, by direct LAD injection of isotope-labelled microspheres (125I) prior to ligation. In the center of the acutely ischemic pig myocardium the residual blood flow, i.e., the myocardial perfusion remaining after LAD occlusion, was 0.01 +/- 0.01 ml/min/g subendocardially and 0.02 +/- 0.01 ml/min/g subepicardially , as estimated with 85Sr-labelled microspheres. These values were significantly lower than the corresponding values for the dog, 0.13 +/- 0.05 ml/min/kg (p less than 0.05) subendocardially and 0.28 +/- 0.08 ml/min/g (p less than 0.01) subepicardially . In the lateral aspects of the ischemic area, calculations of overlap flow were made with the aid of the distribution of the microspheres injected into the LAD. Values of the residual blood flow were normalized and non-ischemic myocardial perfusion was set to 100 units. In subepicardial layers of the myocardium with calculated overlap flows corresponding to 20, 50 or 80 units, respectively, the residual blood flow (overlap flow + collateral flow) actually measured in the pig was 31 +/- 4, 55 +/- 4 and 75 +/- 7 units and in the dog 65 +/- 6, 79 +/- 5 and 91 +/- 2 units. The values for the dog were significantly different from the respective value for the pig (p less than 0.01). In the subendocardial layers the difference between the two species regarding residual blood flow was similar, although the difference was statistically significant only for myocardium with a calculated overlap flow of 80 units. When the calculated overlap flow was subtracted from the measured residual blood flow, the collateral blood flow was found to be extensive in the dog and virtually absent in the pig. When, in the dog, the collateral blood flow across the lateral border of the ischemic area was related to the amount of myocardium it supplies, it was found to be homogeneously distributed. Thus neither subendocardially nor subepicardially could a gradient of collateral blood flow be detected. It is concluded that in the pig the collateral blood flow is almost nil throughout the acutely ischemic myocardium, both in subendocardial and subepicardial layers. In contrast, the dog has an extensive collateral flow. No lateral gradient of this collateral blood flow could, however, be detected.

Neuronal survival and revival during and after cerebral ischemia

Factors influencing survival of neurons during ischemia and neuronal revival after ischemia are reviewed. During ischemia, biochemical and electrophysiological changes depend on residual blood flow rate: below 30 to 40 ml/100 g/min EEG amplitude decreases, below 18 ml/100 g/min spontaneous neuronal activity ceases, and below 10 ml/100 g/min cell membranes depolarize. Attempts to improve blood flow after middle cerebral artery occlusion with vasoactive drugs were not successful but there was an indication that the calcium antagonist nimodipine reduced ischemia-induced disturbances of ion homeostasis. Revival after ischemia depends mainly on post-ischemic hemodynamic factors, such as the no-reflow phenomenon or delayed post-ischemic hypoperfusion. No-reflow was successfully treated by induced hypertension, anticoagulation, and osmotherapy. Delayed post-ischemic hypoperfusion and the associated metabolic disturbances could not be ameliorated by either vasocactive drugs including prostacyclin, nor by metabolic inhibition with barbiturates and hypothermia. The disturbance of metabolic regulation of blood flow during post-ischemic hypoperfusion, therefore, remains one of the main problems of post-ischemic resuscitation.

Accumulation of non-esterified fatty acids in ischemic myocardium in relation to residual blood flow and ATP content

Accumulation of non-esterified fatty acids in ischemic myocardium in relation to residual blood flow and ATP content

The significance of persistent myocardial perfusion during aortic cross-clamping in myocardial protection

Persistent residual myocardial blood flow during aortic cross-clamping can wash out the cardioplegic solution and metabolic end products, continue to deliver substrates, and rewarm the heart. Since microsphere tracers previously used to study “noncoronary” flow could be trapped in the lung before the bronchial circulation reaches the heart, we used xenon 133 washout from the myocardium to determine the residual flow during normothermic cardiopulmonary bypass and aortic cross-clamping. In 16 dogs, with either normal or hypertrophic left ventricles, the persistent myocardial flows during aortic cross-clamping were found to be significant and variable, ranging between 10% and 50% of pre-cross-clamp flows, and were consistently higher in nonvented hearts. The normal hearts with left ventricular venting had residual flow of 13.3 ± 4.0 ml/100 gm/min; those without venting had 37.4 ± 13.0 ml/100 gm/min. The hypertrophic hearts had 9.7 ± 0.7 ml/100 gm/min with venting and 14.1 ± 2.0 ml/100 gm/min without venting. Myocardial biopsy specimens were obtained before and at the end of a 30 minute aortic cross-clamp period, and the myocardial tissue lactate levels were determined. There was an inverse relationship between the magnitude of myocardial residual flow and the tissue lactate accumulation, indicating the metabolic significance of such residual flow. Certain controversies on myocardial protection, which arose due to discrepancies in results obtained from isolated in vitro preparations as compared with those from the in vivo hearts (e.g., the roles of glucose and calcium), may be explained by considering the effects of such residual myocardial flow. Furthermore, the magnitude of myocardial perfusion during aortic cross-clamping can be modulated by a number of maneuvers in order to achieve better myocardial protection during cardiac operations.

Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction.

The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.

Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction.

Regional cerebral blood flow, fractional oxygen extraction and oxygen metabolism have been measured in 34 patients after acute nonhaemorrhagic cerebral hemispheric infarction. Nine cases showed elevated oxygen extraction in the region of the early infarct, and these were the patients studied earliest after the onset of stroke. The results of serial studies to follow the evolution of the pathophysiology of acute stroke in these 9 patients are presented. The elevated oxygen extraction within the early infarct showed a significant reduction over the week following the onset of stroke. The reason for this fall in the fractional use of available oxygen varied in individual cases, and at the extremes was associated with a marked reduction in oxygen metabolism with a further small fall in residual blood flow, or a return of flow without recovery of oxygen metabolism. The significance of oxygen extraction in terms of potential viability of the tissue is discussed. The finding of a lower oxygen extraction in subcortical grey and white matter compared to cortex within the first hours or days of a major stroke is considered indicative of an earlier change from ischaemia to infarction in the deep tissues, probably related to the anatomy of the microvasculature. The interpretation of the results in the light of knowledge accumulated from studies of ischaemia in animals is presented, and problems imposed on data analysis by current limitations in positron emission tomography are discussed.

The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia.

The effects of a calcium antagonist, nimodipine, were tested on the response of the cerebral circulation to arterial pCO2 and blood pressure changes. The effects of reduced blood flow upon oedema formation and extracellular ion homeostasis under nimodipine preloading were studied. Both open and closed skull primate models were used, with alpha-chloralose anaesthesia. Nimodipine infusion increased basal blood flow in the open skull, but not the closed skull animals. Autoregulation to increased blood pressure was little affected. Responses to arterial pCO2 changes and autorerulation to reduced blood pressure were severely imparied. Residual blood flow after middle cerebral artery occlusion was significantly higher with nimodipine than in controls. The threshold levels of blood flow for the development of cortical oedema and for disturbance of ion homeostasis were, however, increased, suggesting that nimodipine interferes with cellular energy metabolism and increases the susceptibility of tissue to ischaemic damage.

Contrast enhancement of myocardial infarction: dependence on necrosis and residual blood flow and the relationship to distribution of scintigraphic imaging agents.

Contrast enhancement of myocardial infarction: dependence on necrosis and residual blood flow and the relationship to distribution of scintigraphic imaging agents.

Calcium ions and calcium antagonists in ischaemia.

The effects of a calcium antagonist, nimodipine, were tested on the response of the cerebral circulation to arterial pCO2 and blood pressure changes. The effects of reduced blood flow upon oedema formation and extracellular ion homeostasis under nimodipine preloading were studied. Both open and closed skull primate models were used, with alpha-chloralose anaesthesia. Nimodipine infusion increased basal blood flow in the open skull, but not the closed skull animals. Autoregulation to increased blood pressure was little affected. Responses to arterial pCO2 changes and autoregulation to reduced blood pressure were severely impaired. Residual blood flow after middle cerebral artery occlusion was significantly higher with nimodipine than in controls. The threshold levels of blood flow for the development of cortical oedema and for disturbance of ion homeostasis were, however, increased, suggesting that nimodipine interferes with cellular energy metabolism and increases the susceptibility of tissue to ischaemic damage.

Role of residual cerebral blood flow on the acute restoration of cerebral blood flow in experimental cerebral ischemia

Role of residual cerebral blood flow on the acute restoration of cerebral blood flow in experimental cerebral ischemia

Detection of pulmonary emboli by positron imaging of inhaled 15O-labeled carbon dioxide

A new radionuclide approach to the scintigraphic detection of pulmonary emboli is described. This method utilizes cyclotron-produced C15O2, administered by inhalation, for rapid labeling of pulmonary blood. Following clearance of oxygen-15 from the lungs by pulmonary blood flow, focal retention of activity results from stasis of blood distal to emboli. On serial positron imaging, focally retained activity delineates embolized pulmonary segments and identifies the location and extent of pulmonary emboli. In animal studies this positron scintigraphic method detected emboli as small as 2 mm in diameter. In patients with suspected pulmonary emboli, this approach appears to be both sensitive and specific. Clinically, C15O2 inhalation imaging is most useful for the detection of pulmonary emboli in patients with chronic lung disease or congestive heart failure. It is rapid and safe and can be easily repeated, with minimal radiation exposure, for determining resolution rates of emboli and for assessing residual blood flow distal to emboli.

Imaging experimental myocardial infarction with indium-111-labeled autologous leukocytes: effects of infarct age and residual regional myocardial blood flow.

The external imaging patterns and the kinetics of infiltration of indium-111 labeled polymorphonuclear leukocytes (PMNs) occurring in the course of the inflammatory response associated with myocardial infarction were studied in dogs subjected to closed-chest anterior wall infarction. The effects of infarct age and regional residual myocardial blood flow upon PMN infiltration were investigated and quantified, and the capacity of indium-111 PMNs to image the experimental infarction was evaluated qualitatively. The epicardial accumulation of indium-111 PMNs occurred primarily in infarct zones with residual blood flow of 0.6 times normal and was maximal (14.8 +/- 3.8 times normal) in the lowest blood flow zone (less than 0.1 times normal). PMN accumulation in the endocardial infarct zones occurred in the regions with blood flow less than 0.6 times normal and was maximal (26.8 +/- 4.9 times normal) in the lowest blood flow zone. However, contrary to the maximal epicardial infiltration period, which occurred within the first 24 hours after infarction, the maximal endocardial infiltration occurred at 72 hours after infarction. In both endocardium and epicardium, PMN uptake was minimal at 120 hours after infarction. In vivo cardiac images were abnormal and revealed discrete, anatomically distinct areas of increased myocardial radioactivity uptake in the anterior wall of all dogs studied within 24--96 hours after infarction. All images obtained 120 hours after infarction were negative. Thus, indium-111 PMNs provide a noninvasive means of in vivo imaging of the inflammatory response to myocardial infarction and allow quantification of this response at a tissue level.

Relationship between the cortical evoked potential and local cortical blood flow following acute middle cerebral artery occlusion in the baboon

In most experimental studies of the effects of ischemia on CNS electrical activity, the ischemia produced has been total. The present experiments, however, were designed to establish quantitatively the changes in electrical activity corresponding to different degrees of cerebral ischemia. The somatosensory evoked potential was measured at various sites on the exposed postcentral gyrus of the anesthetized baboon, and cortical blood flow was assessed in the region of the evoked potential electrode by the highly focal method of hydrogen clearance. The technique of middle cerebral artery occlusion was used to reduce blood flow over the hemisphere. Following occlusion of the artery, the amplitude of the evoked potential typically diminished steadily at a rate depending on the level of residual local blood flow. The rate of depression of the evoked potential amplitude (expressed in units of percent of control per minute) was highly and significantly correlated with the residual flow ( r = −0.95, P < 0.001), which indicated a linear relationship between these variables, the regression line intercepting the flow axis at 15.2 ml/100g/min. The data also strongly suggested a threshold-type relationship between the amplitude of the evoked potential and the local blood flow: If the flow was greater than about 16 ml/100g/min the evoked potential was not affected, but at flows less than about 12 ml/100g/min the evoked potential was abolished.

MESENTERIC ARTERY OCCLUSION WITH INTESTINAL GANGRENE. TWO-STAGE OPERATIVE PROCEDURE WITH THROMBECTOMY, FOLLOWED BY "SECOND LOOK" TO PERMIT RESECTION OF IRREVERSIBLY DAMAGED PORTION OF INTESTINE.

Acute occlusion of the superior mesenteric artery is followed by infarction of the small intestine and ascending colon. The extent of such infarction depends on the localization and size of the (primary or secondary) thrombosis. As the Table shows, the most frequent primary cause is embolism in some authors' experience and thrombosis in others'. In animals, complete interruption of the mesenteric circulation leads to irreversible changes after a period ranging from four hours (Nelson et al, Lillehei et al) to seven hours (Glotzer et al). In man, where some residual blood flow may persist, the intestine is capable of recovery after periods of up to 24 hours following the onset of the crisis, provided the circulation be restored to normal (Shaw et al, Klass, Kleitsch, Miller et al, Saris et al). In animal experiments, Glotzer and co-workers confirmed that the intestinal wall exhibits an astounding power of resistance to ischemia.

Residual blood flow of the kidney after ligation of the main artery: Wolf, H. J., Mohr, M., and Kröger, E.: Ztschr. f. d. ges. exper. Med. 100: 485, 1937

Residual blood flow of the kidney after ligation of the main artery: Wolf, H. J., Mohr, M., and Kröger, E.: Ztschr. f. d. ges. exper. Med. 100: 485, 1937