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Biomedical subjects

J W Fiolet

Publications and source records attributed to J W Fiolet.

At least 37 records · Page 2Linked to original sources
PubMed1988

The cytoplasmic free energy of ATP hydrolysis in isolated rod-shaped rat ventricular myocytes.

The relationship between the percentage of rod-shaped rat heart myocytes and ATP, creatine phosphate, creatine and inorganic phosphate content was determined. With these values the free energy of ATP hydrolysis was calculated and found to be 59.2 kJ/mol, a much higher value than found for the perfused rat heart. When, during the isolation procedure, creatine was present in the perfusion medium during the low-calcium period, the total creatine content of the myocytes after isolation was comparable to that found in the perfused rat heart. However, when creatine was absent during this low-calcium perfusion period, total creatine content of the myocytes was significantly lower. This difference is caused by leakage of creatine from healthy cells. The free energy of ATP hydrolysis was not affected by the absence of creatine during the low-calcium perfusion period.

Adenosine Triphosphate↗
PubMed1988

Distribution of extracellular potassium and its relation to electrophysiologic changes during acute myocardial ischemia in the isolated perfused porcine heart.

An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([K+]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in isolated perfused pig hearts with the use of multiple electrodes. Dispersion of [K+]out is described under three conditions: (1) during regional ischemia in the "central zone" and the "borderzone", (2) during global ischemia, and (3) during perfusion of the heart with a high-K perfusate. Inhomogeneity was greatest during regional ischemia, especially in the borderzone, where generally lower concentrations were measured. When during regional ischemia the normal zone was perfused with a high-K perfusate, dispersion in the ischemic borderzone diminished, and higher concentrations than in the central zone were measured. During global ischemia inhomogeneity was slightly larger than during high-K perfusion. Dispersion during the latter was considered due to experimental error. A decrease in [K+]out during regional ischemia after the initial increase was closely correlated with electrical recovery of the electrograms. This decrease occurred earlier in the borderzone than in the central zone. During ischemia [K+]out was not related to the occurrence of monophasic electrograms, which are indicative of the absence of local regenerative responses. For every single electrode position a linear relationship between TQ depression and [K+]out was found, the slope of which varied with the position of the electrode. When all sites were taken together, there was no correlation between TQ depression and [K+]out. We conclude that: (1) inhomogeneity of K+ is largest in the borderzone, (2) potassium flows from the ischemic zone into the normal zone, (3) transient electrical recovery is related to a decrease (after an initial increase) in [K+]out, which is at least partly due to a flow of K+ toward the normal zone, (4) monophasic ("block") electrograms can be recorded from intrinsically excitable tissue, (5) for every single site in the ischemic region there is a linear relationship between local [K+]out and local TQ segment depression, and (6) the degree of TQ depression at a particular site is not a reliable index of the degree of ischemic injury at that site.

Animals↗
PubMed1987

Myocardial metabolism and coronary sinus blood flow during coronary artery surgery: effects of nitroprusside and nifedipine.

The effects of nitroprusside and nifedipine on hemodynamics, coronary dynamics, and global myocardial metabolism were compared in two groups of patients undergoing elective coronary artery surgery, who were anesthetized with fentanyl, 100 micrograms/kg. After induction of anesthesia, either nitroprusside or nifedipine was started as follows: group S (n = 11) received nitroprusside at an initial rate of 1.3 micrograms/kg/min; group N (n = 9) received nifedipine at an initial rate of 0.7 micrograms/kg/min. Infusion rates were adjusted to maintain systolic blood pressure (SBP) between 80% and 120% of preinfusion (control) values. Control measurements were obtained 10 minutes after intubation. Then vasodilator infusion was started. Additional measurements were obtained 10 minutes after the start of infusion (before surgery) and after sternotomy. The mean (+/- SD) total dose requirements were: nitroprusside, 1.6 +/- 0.3 micrograms/kg/min; and nifedipine 1.1 +/- 0.7 micrograms/kg/min. The mean (+/- SD) total infusion time was: nitroprusside, 32 +/- 5 minutes; and nifedipine, 37 +/- 7 minutes. After 10 minutes of infusion there were decreases in SBP (p less than 0.001) and diastolic blood pressure (DBP; p less than 0.01) in group S. In group N only SBP decreased (p less than 0.01). At this time there were no significant changes in coronary sinus blood flow (CSBF) or myocardial oxygen consumption (MVO2) in either group. After stenotomy DBP remained decreased (p less than 0.05) in group S.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1986

Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation.

The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function.

Blood Flow Velocity↗
PubMed1986

The subendocardial border zone during acute ischemia of the rabbit heart: an electrophysiologic, metabolic, and morphologic correlative study.

Isolated preparations of rabbit interventricular septum were perfused through the coronary arteries with oxygenated Tyrode's solution and placed in a tissue bath where they were superfused as well. Transmembrane potentials were simultaneously recorded from the subendocardium with two flexibly mounted microelectrodes, one from a superficial cell, and the other from a deep cell. Ischemia was produced by stopping coronary flow while superfusion with oxygenated Tyrode's solution was maintained. After a 7 to 12 min ischemic period, the preparation was fixed by coronary perfusion with fixative while the microelectrodes remained in place. After fixation, the microelectrodes were withdrawn. Appropriate tissue blocks were cut in 4 micron serial sections and the microelectrode track was followed until the tip position was identified. Transmembrane potentials during ischemia were divided into two categories: "border zone" potentials (resting membrane potential [RMP] 73 +/- 3 mVe, action potential amplitude [APA] 81 +/- 13 mV, action potential duration [APD] 116 +/- 48 msec, n = 12) and "ischemic" potentials (RMP 53 +/- 4 mV, APA 44 +/- 11 mV, APD 102 +/- 42 msec, n = 8). Ischemic potentials were recorded from cells at depths greater than 560 micron below the endocardial surface and border zone potentials were recorded in a layer at between 130 and 650 micron below the surface. In a separate series of experiments, extracellular concentrations of K+ and pH were measured with ion-sensitive electrodes at different depths and, after a 10 min period of ischemia, part of the septum was placed in liquid nitrogen to allow determination of phosphocreatine (PC) levels in successive 50 to 100 micron layers. After 10 min of ischemia, extracellular K+ gradually increased from 4 to 9 mM in endocardium to a depth of 600 micron, pH fell from 7.4 to 6.6 over the same distance, and PC decreased to very low, stable levels at only 800 micron. It is concluded that in the first 10 min of acute ischemia, an endocardial border zone exists of 40 to 60 cell layers in which transmembrane potentials are affected relatively little by ischemia. Within this electrophysiologic border zone extracellular K+ was lower than 9 mM, pH was higher than 6.6, and tissue content of PC was not lower than 40% of normal. In layers deeper than 600 micron, with further development of a metabolic gradient, action potentials became markedly depressed. This electrophysiologic inhomogeneity within the ischemic subendocardium could be a factor in arrhythmogenesis during the first minutes of ischemia.

Action Potentials↗
PubMed1985

Transmural inhomogeneity of energy metabolism during acute global ischemia in the isolated rat heart: dependence on environmental conditions.

Cardiac energy metabolism is one of the earliest metabolic activities affected when either anoxia or ischemia are induced, as evidenced by the rapid decline of the tissue high-energy phosphate content of creatinephosphate (CrP) and ATP. Several reports deal with the spatial inhomogeneity of these changes and it is generally found, that the subendocardium is more sensitive to ischemia than the subepicardium. The metabolic transmural gradients observed during in vivo ischemia were attributed to both variations in wall tension and collateral flow. Lowe et al. recently presented evidence that in addition to these variations the higher vulnerability of the subendocardium to ischemia could be secondary to an increased metabolic rate.

Adenosine Triphosphate↗
PubMed1984

The change of the free energy of ATP hydrolysis during global ischemia and anoxia in the rat heart. Its possible role in the regulation of transsarcolemmal sodium and potassium gradients.

The timecourse of change of the cytoplasmic free energy of ATP hydrolysis during acute global ischemia and during anoxic perfusion was determined in the isolated rat heart. The timecourse of change of transsarcolemmal Na+ and K+ gradients during anoxia, and of extracellular K+ during ischemia were measured. The free energy of ATP hydrolysis was calculated from the equilibrium of the creatinekinase reaction, taking into account the pH-dependence of the equilibrium constant, and intracellular inorganic phosphate. In control aerobic hearts the mean free energy of ATP hydrolysis was 55.2 kJ/mol. Both during ischemia and anoxia it declines biphasically. The first rapid phase terminates within 4 min into a plateau of about 46 kJ/mol. The duration of this plateau is shorter during anoxia than during ischemia. The second phase of decrease starts after 6 to 8 min during anoxia and after 15 to 20 min during ischemia. After 30 min of anoxia the free energy of ATP hydrolysis has decreased to 31 kJ/mol and after 30 min of ischemia a value of 35.5 kJ/mol is reached. The timecourses of change of measured intracellular Na+ and K during anoxia and of extracellular K+ during ischemia were also biphasic. During anoxia the loss of intracellular K+ was almost equal to the gain of intracellular Na+ at any point. Based on the assumption that the sodium pump is in thermodynamic equilibrium or near-equilibrium during anoxia and ischemia, the time-course of change of Na+ and K+ gradients during anoxia and of extracellular K+ during ischemia were calculated from the respective timecourses of change of the free energy of ATP hydrolysis. Good agreement was observed between calculated and measured changes of Na+ and K+ gradients. It is concluded that the magnitude and direction of change of transsarcolemmal ion-gradients during anoxia and ischemia may be under direct thermodynamic control of myocardial energy metabolism.

Adenosine Triphosphate↗
PubMed1983

The definition of myocardial infarction during aortocoronary bypass surgery.

In a study of 392 aortocoronary bypass (CABG) patients, we found 16 patients with a postoperative new Q wave, 29 patients with new intraventricular conduction disturbance, 17 patients with cardiogenic shock, and 14 patients with excessive CK-MB activity. Those criteria were considered as diagnostic of perioperative acute myocardial infarction (AMI). Listing the 392 patients in a Venn diagram: five patients had three positive criteria, eight had two, 43 had one, and 336 had none. Ventricular arrhythmia, supraventricular arrhythmia, or ST-T changes occurred in decreasing frequency in patients with a decreasing number of positive criteria. Five patients died postoperatively and in four a postmortem examination was available. Diagnostic criteria partly predicted autopsy findings. We conclude that the diagnostic criteria of perioperative myocardial infarction have a low diagnostic performance.

Adult↗
PubMed1983

beta-Blockade and acute myocardial infarction.

Results from experimental and clinical studies suggest that beta-blockade may have beneficial effects in acute myocardial infarction. These effects relate to decrease of cardiac work and improvement of metabolism without deleterious effects on perfusion of the ischemic myocardium. Several well designed randomized controlled studies with beta blockers have been carried out in the acute phase of myocardial infarction. Although beneficial effects could be demonstrated in some subsets, most studies however included small numbers of patients, thus indicating that more large scale studies are necessary to assess the efficacy of beta blockers in reducing infarct size and hospital mortality.

Acute Disease↗
PubMed1983

Infarct size estimation from serial CK MB determinations: peak activity and predictability.

In 198 patients with acute myocardial infarction serial measurements of plasma creatine kinase isoenzyme MB (CK MB) were performed at four hour intervals. In every patient, maximal CK MB activity (peak activity) was compared with calculated total release per litre plasma. In 28 patients (group 1) sufficient plasma samples were available for calculation of the apparent first order inactivation constant kd. Mean apparent kd in group 1 patients was 0 . 085 +/- 0 . 018 h-1 (mean +/- SD). Total release in group 1 was calculated with individual apparent kd values (Q) and with the mean kd value (Q*). In the remaining 170 patients (group 2), Q* only was calculated. A linear relation between peak activity P and total release (both Q and Q*) was found, extending over the whole range of CK MB peak activities that are routinely observed (4-216 U/l). It was immaterial whether a one or a two compartment model was used: both yielded a close linear relation. Though the mean ratio between Q* and peak activity depends on the value of kd chosen for calculation of total release (the ratio increasing with increasing kd), linearity between peak activity and Q* was found for any value of kd up to 0 . 4 h-1. In group 1, shapes of calculated CK MB release curves Q*(t), expressed relative to maximal release Q(40), were sufficiently similar so as to be superimposable; the section of the release curves extending from 12 hours before until two hours after peak time could be tentatively described by a linear time course with a slope of 4 . 2 +/- 0 . 5% per hour (mean +/- SD). We conclude that peak activity of CK MB is a reliable estimate of cumulative CK MB release and may be clinically more practicable than calculation of Q(40). Both the similarity and the large apparently linear section of the calculated enzyme release curves possibly permit early prediction of Q(40), with acceptable precision.

Creatine Kinase↗
PubMed1983

Boehringer immunoinhibition procedure for creatine kinase-MB evaluated and compared with column ion-exchange chromatography.

In determination of creatine kinase isoenzyme MB (CK-MB), the Boehringer immunoinhibition method gives a high and variable blank activity as compared with column-chromatography. Thus a correction must be applied. Furthermore, a second correction of 1% of total creatine kinase activity is necessary to compensate for nonspecific creatine phosphate-dependent activity. As a consequence, two immunoinhibition determinations--one for CK-MB and one for blank activity--and a determination of total creatine kinase are required. Use of the manufacturer's diagnostic criteria, on the basis of which suspected myocardial infarction is confirmed or eliminated, leads to a high frequency of false-negative conclusions.

Chromatography, Ion Exchange↗
PubMed1980

Evaluation of a radioenzymic kit for determination of plasma catecholamines.

We evaluated a commercially available reagent test-kit (Upjohn) for simultaneously determining norepinephrine, epinephrine, and dopamine in 50-microL of plasma. The three catecholamines are enzymically converted into the radioactive O-methyl derivatives and separated by thin-layer chromatography. Day-to-day precision (CV) was 11, 10, and 14% for norepinephrine, epinephrine, and dopamine, respectively. The relationship between concentration of catecholamine and radioactivity (net dpm) was linear to at least 8 ng (corresponding to 1 mumol/L in plasma). Sensitivity was approximately 2 pg for dopamine, 1 pg for each of the other two catecholamines. Under our conditions, epinephrine was not quite completely resolved from the other two fractions. Catecholamine values determined in normal humans, after 30 min supine and after normal laboratory activity, agreed well with those found by other investigators. Correlation was good between kit results and those obtained in another laboratory that used self-prepared reagents and "high-performance" liquid chromatography for the separation.

Catecholamines↗