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Biomedical subjects

J Jehle

Publications and source records attributed to J Jehle.

At least 19 recordsLinked to original sources

Effects of anesthesia on functional activation of cerebral blood flow and metabolism.

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMR(glc)) induced by functional activation is generally carried out in animals under anesthesia, usually alpha-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with alpha-chloralose the effects of vibrissal stimulation on lCMR(glc) and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMR(glc) responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions.

Anesthesia, General↗

[Circular hemorrhagic subendocardial necrosis after heart arrest and resuscitation].

A 19 year old boy, previously healthy suffered a cardiac arrest by getting up. Ten minutes afterwards the general practitioner commenced cardiopulmonary resuscitation, 15 minutes later ventricular fibrillation developed and the emergency physician carried out intubation and repeated defibrillation. During the next few hours a stabilization of the circulatory system was achieved. Five days after the cardiac arrest brain death occurred. The postmortem findings on the heart (only a heart section was performed) showed extensive circular hemorrhagic subendocardial necrosis with initial organization of the left ventricular wall and the septum with a well-preserved subendocardial area. In the right ventricular wall only a few small areas of organization were observed. All lesions were consistent with the cardiac arrest suffered 5 days previously. The morphological changes differ from those of a usual hemorrhagic infarction and of the sequences of a cardiopulmonary resuscitation. The circular subendocardial necroses occur after a cardiac arrest which exceeds the resuscitation time of the heart. They do not respect the area of coronary distribution and their hemorrhagic component develops after successful reanimation within the necrotic myocardium.

Adult↗

Direct percutaneous transluminal coronary angioplasty in acute myocardial infarction. Predictors of short-term outcome and the impact of coronary stenting. Study Group of The Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK).

BACKGROUND: Direct percutaneous transluminal coronary angioplasty (PTCA) is widely accepted in the treatment of acute myocardial infarction since excellent results had been reported from several small randomized trials. Less favourable results were observed in large-scale registries. In particular, the use of stents in acute myocardial infarction has become common practice without documented evidence of clinical efficacy. METHODS: Data were analysed from a registry of all consecutive percutaneous transluminal coronary angioplasty procedures from 62 centres in Germany, including 2331 direct percutaneous transluminal coronary angioplasty in acute myocardial infarction from July 1994 to April 1997. RESULTS: The overall angiographic success rate of percutaneous transluminal coronary angioplasty, defined as complete antegrade perfusion of the infarct vessel, was 87%. In-hospital mortality was 11.2%. The most important predictor of death was the presence of cardiogenic shock in 15% of patients, of whom 52% died. Mortality in patients without shock was 3.9%. Failed percutaneous transluminal coronary angioplasty was associated with a mortality of 36%. Further independent predictors of death were older age, multivessel disease, and anterior myocardial infarction. Stents were used in 4.1% of the procedures in 1994, increasing to 53% in 1997. However, this was not accompanied by improved clinical outcome. Mortality with coronary stenting was 9.9% vs 11.6% without stents (ns). CONCLUSIONS: Direct percutaneous transluminal coronary angioplasty is a valuable treatment strategy in acute myocardial infarction, although the results are less exceptional than reported from some highly specialized centres. Failed percutaneous transluminal coronary angioplasty seems to be harmful, thus outweighing much of the benefit from successful procedures. Stents did not improve the clinical outcome significantly, despite technically successful placement in 98%. Mortality from cardiogenic shock continues to be excessively high despite direct PTCA.

Adult↗

Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose.

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose.

Animals↗

Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats.

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mumol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mumol/L glibenclamide, and almost complete blockade (+5%) with 2 mumol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.

Animals↗

Preservation of autoregulatory cerebral vasodilator responses to hypotension after inhibition of nitric oxide synthesis.

Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular autoregulatory vasodilator response to hypotension were studied in conscious rats. Cerebral blood flow (CBF) was determined with [14C]iodoantipyrine in a saline-treated control group and in three groups following inhibition of NO synthase activity by twice daily intraperitoneal injections of 50 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) for four days. In the saline-control group (n = 8) and in the L-NAME-treated Group (a) (n = 8) CBF was determined while systemic mean arterial blood pressure (MABP) remained at its resting level (means +/- S.D., 128 +/- 6 and 151 +/- 11 mmHg, respectively). In the other groups CBF was determined after MABP was reduced by blood withdrawal to 118 +/- 9 and 88 +/- 8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated MABP, global CBF was significantly lower in L-NAME-treated Group (a) than in the saline-controls (P < 0.005), indicating cerebral vasoconstriction resulting from inhibition of NO synthesis. Global CBF was not significantly reduced further in the two groups with hypotension. Local CBF in the hypotensive rats showed no significant reductions below values in L-NAME-treated control rats (Group (a)) in 31 of 32 brain structures; the only exception was in the auditory cortex of the severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral vasodilatation to compensate for reduced arterial blood pressure is maintained following inhibition of NO synthesis.

Animals↗

Role of the cerebellar fastigial nucleus in the physiological regulation of cerebral blood flow.

Local cerebral blood flow (ICBF) was measured with [14C]iodoantipyrine in conscious, unrestrained rats during electrical stimulation of the fastigial nucleus (FN). Electrode position in the FN was determined by blood pressure (MABP) responses to stimulation under anesthesia. In nine rats in which MABP responses had been variable under anesthesia, bipolar stimulation (50 Hz, 0.5 ms, 1 s on/1 s off) with currents of 30-100 microA after recovery from anesthesia produced stereotypic behavior but little effect on MABP and ICBF. In seven other conscious rats currents could be raised to 75-200 microA without inducing seizures, resulting in sustained MABP elevations during the ICBF measurement and significantly increased ICBF in the sensory-motor (+45%), parietal (+31%), and frontal cortices (+56%) and the caudate-putamen (+27%) above control values (n = 9). Glucose utilization, measured with [14C]deoxyglucose, in rats similarly stimulated was significantly increased in six structures, including some of the above, indicating increases in ICBF due to metabolic activation. Unilateral or bilateral electrolytic lesions of the FN, placed 6-7 days before ICBF measurement, had negligible effects on resting ICBF and on autoregulation in conscious rats. These results fail to support a specific role for the FN in physiological regulation of cerebral blood flow in unanesthetized rats.

Anesthesia↗

Lack of effects of inhibition of nitric oxide synthesis on local glucose utilization in the rat brain.

The effects of chronic treatment with NG-nitro-L-arginine methyl ester, a potent inhibitor of nitric oxide synthase activity, on local cerebral glucose utilization were examined in conscious rats. Intraperitoneal injections of 50 mg/kg of the nitroarginine twice daily for 4 days have been found to result in almost complete inhibition of nitric oxide synthase activity in brain. Local cerebral glucose utilization was determined by means of the quantitative autoradiographic [14C]deoxyglucose method in an experimental group (n = 7) of rats that were treated with the nitroarginine according to this schedule and in a normal control group (n = 7) treated similarly with saline. The rats were conscious but partially restrained during the determinations of local cerebral glucose utilization. The nitroarginine treatment raised mean arterial blood pressure statistically significantly to 147 +/- 3 mm Hg (mean +/- SEM) from a level of 120 +/- 5 mm Hg in the saline controls (p < 0.001 by grouped t test), but there were no statistically significant effects on glucose utilization in any of 39 brain structures examined. It is concluded that nitric oxide normally exerts no significant influence on energy metabolism in the rat brain.

Animals↗

Rates of local cerebral protein synthesis in the rat during normal postnatal development.

The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPSleu) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPSleu were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were approximately 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPSleu increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPSleu were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination.

Aging↗

[Correlations between arrhythmias and left ventricular function at rest and during stress in patients with postinfarct aneurysm].

The results (clinical, hemodynamic, and angiographic data) of 197 patients with left ventricular anterior wall aneurysm were evaluated at rest and during exercise (bicycle ergometer) 6 months after the acute infarction. Using the technique of digital subtraction angiography, left ventricular volumes were estimated after injection of contrast medium into the pulmonary artery and measuring of pulmonary artery pressure. In 136 patients a programmed right ventricular stimulation was performed additionally. The patients were divided into the following groups: patients with (VT+) and without (VT-) ventricular arrhythmias in history. Group VT- was subdivided in patients with positive (RV+) or negative (RV-) result of right ventricular stimulation. In group VT+ chamber volumes were greater and ejection fraction was smaller than in group VT-. At rest the results of subgroup RV+ were similar to group VT+, but during exercise similar to group RV-. These results show that left ventricular function at rest and during exercise is much more impaired in patients with spontaneous and by stimulation-induced arrhythmias than in patients without these arrhythmias. The conclusions for clinical practice of these findings are not yet clear, concerning, for example, the prophylactic use of antiarrhythmic measurements in patients without spontaneous but with induced arrhythmias. Further investigations (long-term follow-ups of these patients) will be necessary.

Arrhythmias, Cardiac↗

[Malignant hemangioendotheliosarcoma in the area of the right coronary artery: imaging by selective coronary angiography].

We report on a case of a malignant hemangioendotheliosarcoma in the right coronary artery. The first manifestation was a pericardial tamponade from a hemorrhagic pericardial effusion. The diagnosis was established only by selective coronary angiography of the right coronary artery, other imaging procedures did not lead to the diagnosis. During follow-up, multiple angiosarcoma developed in the liver, the spleen and, finally, in the lungs. Despite multichemotherapy, the patient died 7 months after the first manifestation.

Biopsy↗

[The determination of myocardial perfusion parameters from coronary angiograms by analysing the passage of contrast media through the myocardium].

Digital subtraction angiography allows to record the passage of contrast material through the myocardium as a time-intensity curve, the so-called densogram. Temporal changes of contrast material in a region of interest are described by a differential equation. The free parameters of this model equation are determined by a curve-fitting procedure. Four parameters of the model equation are expected to be connected with myocardial perfusion. We intended to verify this assumption by comparing changes in coronary blood flow (CBF) with changes of the different parameters. The angiograms of 9 patients without coronary artery disease were studied before and after intravenous application of dipyridamole. Changes in CBF were assessed by a videodensitometric method. Linear regressions between changes of CBF and the parameters of the differential equation show the following results: one parameter of the model equation--the ratio of regional blood flow and regional volume--remarkably underestimated CBF changes. This can be explained by an increase of regional blood volume after increased CBF due to dipyridamole. However, a close correlation was found between CBF changes and the remaining parameters. This study suggests that digital measurements from coronary angiograms using the presented model equation provide a means of assessing myocardial perfusion.

Adult↗

[The reliability of angiographic volume determination of the left ventricle using digital image subtraction--significance in stress tests].

Using the technique of digital subtraction angiography (DSA), left ventricular volumes can be determined after intravenous injection of contrast medium at rest and during exercise. The significance of the well known errors of angiographic determination of left ventricular volumes was investigated in 22 patients before and during a bicycle exercise test. Before and after exercise 40 ml of contrast medium were injected (18 ml/s) intravenously to calculate left ventricular volumes. Enddiastolic and endsystolic contours of the left ventricle were traced by two investigators (A and B) on five different days. Using these contours, volumes were calculated by a computer system. The first calculation of both investigators (single measurement) and the mean value of all five calculations (repetitive measurements) were compared. In the same procedure left ventricular contours of six patients were calculated after conventional contrast ventriculography (40 ml of contrast medium). No systematic deviations were found in comparing the results of both investigators using the single or repetitive method by means of DSA: (VolB = 0.86 VolA + 12.2, r = 0.97 versus VolB = 0.96 VolA + 9.1, r = 0.99). Compared to single method the residuals (Syx) of the repetitive method were significantly smaller: Syx = +/- 16.3 ml vs +/- 8.9 ml (p less than 0.01). Similar results were found in conventional ventriculography: single method Syx = +/- 18.7 ml and repetitive method Syx = +/- 8.8 ml (p less than 0.01). Comparing the volumes determined by DSA and by conventional ventriculography, respectively, no significant differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Measurement of local cerebral blood flow with [14C]iodoantipyrine in the mouse.

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.

Animals↗

[Systolic and diastolic blood flow velocities in the left coronary artery before and following i.v. dipyridamole. Comparative measurements using a digital image processing in 2 unstenosed vessel branches].

The hemodynamic significance of coronary artery stenoses cannot be assessed by presently-used methods. Especially stenoses of small and moderate degree only reveal hemodynamic relevance during augmentation of coronary flow. It can be expected that the increase in flow is limited in a stenotic branch, compared with an unstenosed branch of the same vessel. The increase in coronary blood flow in two unstenosed branches of the same vessel, however, should be nearly identical. To prove this hypothesis, the relative increase in coronary flow was measured in two unstenosed branches of the left coronary artery by means of digital subtraction angiocardiography. Ten patients were examined before and after intravenous administration of 20 mg (on average 0.29 mg/kg body weight) dipyridamole. Dipyridamole resulted in an increase in the diameter of the left anterior descending branch (LAD) of 11% (p less than 0.005) and of the circumflex artery (RCx) of 13% (p less than 0.005). The increase in flow velocity during systole amounted to 49% in the LAD (p less than 0.001) and to 58% in the RCx (p less than 0.005); during diastole to 60% in the LAD (p less than 0.005) and 83% in the RCx (p less than 0.005). The increase in volume flow during systole amounted to 78% in the LAD (p less than 0.005) and to 89% in the RCx (p less than 0.005), during diastole to 84% in the LAD (p less than 0.005) and to 113% in the RCx (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗