Biomedical subjects

R Coronel

Publications and source records attributed to R Coronel.

62 records · Page 4Linked to original sources

PubMed1987

Relationship between extracellular potassium accumulation and local TQ-segment potential during acute myocardial ischemia in the porcine.

Depolarization of resting membrane potential during acute myocardial ischemia is strongly correlated with the accumulation of extracellular potassium ([K+]e). Also, diastolic currents of injury flowing across the ischemic border that occur as a result of local differences in resting membrane potentials cause changes in the TQ-segments of unipolar, DC-coupled, extracellular electrograms. Further, the changes in [K+]e and TQ-segment potentials during acute ischemia and reperfusion follow a similar time course. For these reasons, a predictable relationship between [K+]e and TQ potentials might be expected to exist. If found, easily obtainable local TQ potential measurements could serve as an index of the resting membrane depolarization induced by [K+]e accumulation and, by extension, as an index of ischemic injury. We measured local [K+]e and TQ potentials from 30 mid-myocardial sites in central and marginal ischemic zones in 2 isolated, Langendorff-perfused porcine hearts during a single, 10-min ligation of the left anterior descending coronary artery. In general, we found a linear relationship between [K+]e and TQ potential for both ischemic zones when data was taken as a whole, but the slopes (S) and correlation coefficients (R) were markedly different between the two locations (-2.24 vs -1.28 and -0.73 vs -0.51 for central and marginal zones, respectively). Further, we found a time dependent change in both S and R that was biphasic. Both were low during the first minutes, attained their maximum values at 4 mins, and then fell during the remainder of the occlusion. We conclude, therefore, that local TQ potentials cannot be used as an index of the severity of ischemic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1986

Electrophysiological basis for arrhythmias caused by acute ischemia. Role of the subendocardium.

The major electrophysiological changes during the first 10 min of myocardial ischemia caused by complete obstruction of a coronary artery are a reduction in membrane potential, a decrease in action potential amplitude and upstroke velocity, and a prolongation of recovery of excitability following an action potential. Conduction velocity in the direction parallel to the long axis of myocardial fibers (VL) and in the transverse direction (VT) in normal myocardium are in the order of 40 cm/s and 20 cm/s respectively. During ischemia, conduction velocity decreases and lowest values for VL are in the order of 20 cm/s, for VT around 10 cm/s, before the ischemic tissue becomes inexcitable. Calculated dimensions of a possible re-entrant circuit in acutely ischemic myocardium (the product of refractory period and conduction velocity) are in the order of 7 to 8 cm. Re-entrant circuits of such dimensions were indeed demonstrated by simultaneous recording of 125 extracellular potentials from the epicardial surface of the ventricles during spontaneously occurring ventricular arrhythmias after coronary occlusion. Previous studies provided evidence that premature ventricular depolarization which initiate re-entry originated in the subendocardium, and the present experiments confirmed this. Destruction of the subendocardium of isolated, Langendorff perfused canine hearts, including the Purkinje system, by intracavitary application of phenol, did not, however, abolish ectopic activity during either ischemia or reperfusion, although the nature of the arrhythmias during ischemia was different from those in intact hearts. Coupling intervals of ectopic beats were longer in phenol-treated hearts than in intact hearts, but the site of origin of initial ectopic beats leading to ventricular tachycardia could not be determined. Re-entrant circuits with revolution times in the order of 340 to 400 ms accounted for the slow tachycardias observed in phenol-treated hearts. In contrast to intact hearts, these tachycardias never degenerated into ventricular fibrillation, indicating that an intact Purkinje system may be a necessary requirement for ventricular fibrillation to occur during acute, regional myocardial ischemia.

Animals↗

PubMed1986

Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.

Conduction velocities along longitudinal (vL) and transverse (vT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. In some of the experiments extracellular [K+] ([K+]o) and transmembrane potentials were recorded. During normal perfusion vL and vT were (cm/sec) 50.08 +/- 2.13, (SE) and 21.08 +/- 0.97. After 3 to 5 min of global ischemia, vL and vT decreased to approximately 30 and 13 cm/sec. Before the occurrence of total inexcitability propagation became time dependent 2: 1 block developed and centrifugal spread from the stimulus site was partially blocked at short intervals and was normal at long intervals. This suggested that slowed conduction was dependent on spatial nonuniformities of recovery from excitability. Slowing of conduction during ischemia was not explained by accumulation of [K+]o alone, because vL and vT at a given [K+]o were lower during ischemia than during perfusion with elevated K+. In hearts perfused at 20 mM [K+]o "slow responses" were produced by addition of epinephrine (2.5 X 10(-5)M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: the large diameters of reentrant circuits and the beat-to-beat changes in localization of conduction block.

Action Potentials↗

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

Variability of recovery of excitability in the normal canine and the ischaemic porcine heart.

Normal hearts: Refractory periods were determined at 12 to 15 intramural sites of the normal canine left ventricle during steady state regularly driven rates, after each of a series of four early premature beats, and after a long pause following a series of three premature beats. The dispersion in recovery of excitability, defined as the standard deviation of the mean refractory periods, was in absolute terms the same for all three situations. However, since mean refractory periods shortened after premature beats, in relative terms, dispersion of recovery of excitability was greatest after a series of four premature beats. The refractory periods of the specialized conducting system determined during the initial beats of a new, faster rate, showed that in subsequent beats, the refractory periods of the bundle branches are alternatively shorter and longer than the refractory period of the ventricular myocardium. An example of 'concealed bundle branch re-entry' is shown. It is concluded that normal hearts are well protected from sustained arrhythmias induced by changes in rate and rhythm. Ischaemic hearts: In isolated, Langendorff perfused porcine hearts, regional ischaemia was produced by clamping the left anterior descending coronary artery. The transmembrane potentials then were recorded within a distance of less than 1 mm from a stimulating electrode in the ischaemic zone. Refractory periods in the central ischaemic zone lengthened, those in the border zone shortened. Recovery of excitability in an ischaemic myocardium cannot be expressed in terms of intervals between stimuli alone: the quality of the premature response must also be taken into account. Typically, responses elicited well after completion of repolarization have markedly reduced amplitudes and upstroke velocities. Thresholds for stimulation increase in an ischaemic myocardium, and the use of strong test stimuli leads to artefactual results: evidence is presented that strong premature stimuli excite less injured cells far away from the stimulus site. Premature stimuli often induced arrhythmias. Presence of local responses in central ischaemic cells suggest regions of unidirectional block, creating circumstances where re-entry may occur. After a long pause, alternation in action potential amplitude and duration became more pronounced: possibly, a premature impulse elicited after a long pause encounters more regions of unidirectional block so that re-entry is facilitated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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↗

PubMedDate not supplied

Osmotic changes and transsarcolemmal ion transport during total ischaemia of isolated rat ventricular myocytes.

Transsarcolemmal water and ion movement during 1, 7.5, 15, and 30 min of total ischaemia was studied in suspensions of isolated rat ventricular myocytes, with a control ratio of about 1 of intracellular volume (ICV) to extracellular volume (ECV). In this preparation, contrary to the intact heart: 1) There is no external exchange of matter, 2) the sum of ICV and ECV remains constant and 3) ECV is homogeneous; no separate interstitial and intravascular compartments are present and no extracellular metabolite or ion gradients develop as may occur in the intact heart. We demonstrate that: 1) It is possible to make an ischaemic preparation of isolated myocytes with a procedure which causes only minimal mechanical damage to intact myocytes. The preparation allows measurement of ECV with the non-cardiac enzyme alpha-amylase as a macromolecular extracellular marker. 2) The time course of change of metabolites relevant to energy metabolism (creatinephosphate (CrP), creatine (Cr), ATP, ADP, inorganic phosphate P(i) and lactate) is similar to that in the intact heart. 3) ECV has decreased and ICV increased by about 20% after 30 min of ischaemia. 4) Extracellular [Na+], [K+], [Cl-], and [P(i)] increase, but not in proportion to the decrease of ECV. There is net efflux of K+, P(i), H+, and lactate-; efflux of K+ and P(i) is quantitatively much less than influx of Na+ and Cl-. 5) Measured extracellular osmolality has increased with up to 70 mOsm/l after 30 min of ischaemia. The increase of extracellular [lactate-], [Na+], [K+], [Cl-], [P(i)] and the decrease of [glucose] account for the change of osmolality measured. 6) Summation of the electrical charges associated with measured increase of extracellular [lactate-], [Na+], [K+], [Cl-], [P(i)] shows a surplus of negative charge, which almost equals extracellular [lactate-], suggesting an equally large increase of osmotically inactive H+ as the compensatory ion. 7) Blockade of anaerobic metabolism with iodoacetic acid (IAA) reduces efflux of lactate and P(i) but greatly amplifies influx of sodium and chloride and efflux of potassium.

Animals↗

PubMedDate not supplied

Transmural inhomogeneity of extracellular [K+] and pH and myocardial energy metabolism in the isolated rat heart during acute global ischemia; dependence on gaseous environment.

We investigated in the isolated rat heart the influence of the gas surrounding the globally ischemic heart on transmural inhomogeneity of energy metabolism, extracellular K+ accumulation, and change of extracellular pH. Hearts were made ischemic in 100% N2 (N2-ischemia), 100% O2 (O2-ischemia) or 100% CO2 (CO2-ischemia). We measured: 1) Midmural, subepicardial, and epicardial changes of extracellular [K+] and pH during successive 6-min periods of global ischemia, and 2) content of creatinephosphate (CrP) in consecutive tissue sections of 100 microns, from the subepicardium after 10 min of ischemia. A) During O2-ischemia both extracellular [K+] and change of pH in the subepicardium are significantly less than in the midmyocardium. During N2-ischemia only minor differences exist in [K+] and pH between the subepicardium and the midmyocardium. During CO2-ischemia midmural and subepicardial [K+] are similar to those during N2-ischemia. The midmural change of pH resembles that during N2-ischemia; subepicardial change of pH, however, was slightly larger. Midmural changes in [K+] and pH were not influenced by the nature of the surrounding gas. B) After 10 min of O2-ischemia a gradient of tissue content of CrP extends from the epicardium (CrP about 30 mumoles/g dry weight) to a distance of about 1000 microns (CrP 1 mumoles/g dry weight). In N2- and CO2-ischemia a CrP gradient is absent; CrP is appreciably less than 1 mumoles/g dry weight at any distances from the epicardium. C) We conclude that diffusion of O2 into the myocardium and of CO2 from the myocardium affects transmural gradients of [K+], pH, and energy metabolism during ischemia. Local availability of O2 increases the capacity of the ischemic tissue to generate high energy phosphates and mitigates ischemia-induced changes of transsarcolemmal ion gradients.

Acid-Base Equilibrium↗