High resistance to lipid peroxidation of bird heart mitochondria and microsomes: Effects of mass and maximum lifespan.

The aim of this investigation was to study the connection between body size, fatty acid composition and sensitivity to lipid peroxidation of heart mitochondria and microsomes isolated from different size bird species: manon (Lonchura striata), quail (Coturnix coturnix var japonica), pigeon (Columba livia), duck (Cairina moschata) and goose (Anser anser), representing a 372-fold range of body mass. Fatty acids of total lipids were determined using gas chromatography and lipid peroxidation was evaluated with a chemiluminescence assay. The fatty acids present in heart organelles of the different bird species analyzed showed a small number of significant allometric trends. In mitochondria, from the individual fatty acid data, palmitoleic acid (C16:1 n7) increased allometrically (r=0.878), while stearic acid (C18:0) was negatively related to body mass (r=-0.903). Interestingly, none of the calculated fatty acid variables, the average fatty acid saturated, monounsaturated, polyunsaturated (PUFA) and the unsaturation index (UI) was established to show significant body size-related variations. In heart microsomes, the content of C18:0 was significantly smaller (r=-0.970) in the birds of greater size. A significant allometric increase in linoleic acid (C18:2 n6) (r=0.986), polyunsaturated (r=0.990) and UI (r=0.904) was observed in the larger birds. The total n6 fatty acids of heart mitochondria did not show significant differences when it was correlated to body mass of the birds. Moreover, positive allometric relationships were shown for microsomes. The total n3 fatty acids of heart mitochondria and microsomes indicated no significant correlations to body mass of birds. The C16:1 n7, C18:0 in mitochondria and C18:0, C18:2 n6, PUFA, UI and PUFA n6 in microsomes showed significant differences when they were correlated to maximum life span (MLSP) of birds. As light emission=chemiluminescence originated from heart organelles was not statistically significant, a lack of correlation between the sensitivity to lipid peroxidation and body size or maximum life span was obtained. These results indicate that the high resistance of bird hearts to the attack by free radicals is body size-independent and would be related to the preservation of cardiac function.

An allometric study of fatty acids and sensitivity to lipid peroxidation of brain microsomes and mitochondria isolated from different bird species.

The objective of this investigation was to examine the relationship between body size, fatty acid composition and sensitivity to lipid peroxidation of mitochondria and microsomes isolated from the brain of different size bird species: manon, quail, pigeon, duck and goose, representing a 372-fold range of body mass. Fatty acids of total lipids were determined using gas chromatography and lipid peroxidation was evaluated using a chemiluminescence assay. The allometric study of the fatty acids present in brain mitochondria and microsomes of the different bird species showed a small number of significant allometric trends. In mitochondria the percentage of monounsaturated fatty acids, was significantly lower in the larger birds (r=-0.965; P<0.008). The significant allometric increase in 18:2 n-6; linoleic acid (r=0.986; P<0.0143), polyunsaturated (r=0.993; P<0.007) and total unsaturated (r=0.966; P<0.034) in brain microsomes but not in mitochondria may indicate a preferential incorporation of this fatty acid in the brain endoplasmic reticulum of the larger bird species. The brain of all birds studied had a high content of docosahexaenoic acid. However brain mitochondria but not microsomes isolated from all the birds analyzed showed a significant decrease of arachidonic and docosahexaenoic acids during lipid peroxidation. The allometric analyses of chemiluminescence were not statistically significant. In conclusion our results show absence of correlation between the sensitivity to lipid peroxidation of brain mitochondria and microsomes with body size and maximum life span.

Comparison of the protective effects of ischemic preconditioning and the Na+/H+ exchanger blockade.

The protective effects of ischemic preconditioning (IP) and Na+/H+ exchanger blockade (NHEb) by two blockers [ethylisopropylamiloride (EIPA) and HOE 642] were compared in the isovolumic perfused rat heart. The impairment in systolic and diastolic function detected in control ischemic hearts (C) exposed to 20 min of ischemia and 30 min of reperfusion was diminished in similar extent by IP and by NHEb with EIPA and HOE 642. At the end of the reperfusion period +dP/dtmax values were 57+/-9% in C hearts and 94+/-6%, 82+/-6% and 104+/-6% after IP and NHEb with EIPA and HOE 642, respectively. A depletion of ATP levels detected in C hearts after reperfusion (from 20.2+/-0.8 micromol/g dry weight before ischemia to 6.9+/-0.7 micromol/g dry weight) was partially prevented by both IP and NHEb with EIPA (9.2+/-0.7 micromol/g dry weight and 11.1+/-0.5 micromol/g dry weight, respectively). The ischemic contracture (IC), assessed by the left ventricular end diastolic pressure (LVEDP), observed in C hearts (35+/-4 mmHg) was not decreased by IP (40+/-4 mmHg) but it was prevented by NHEb (18+/-4 mmHg and 10+/-3 mmHg with EIPA and HOE 642, respectively). The ATP levels at the end of the ischemic period were similar in C and IP hearts (4.1+/-0.2 micromol/g dry wt vs. 3.3+/-0.4 micromol/g dry wt) but they were significantly higher after NHEb with HOE 642 (7.0+/-1.0 micromol/g dry wt). PKC inhibition by chelerythrine abolished the protection induced by IP after reperfusion although not the improvement induced by NHEb with EIPA. According to the present results, we can conclude that despite the fact that IP and NHEb are protecting the postischemic function in a similar magnitude, both interventions are different in terms of modifying IC that develops during the ischemic period. IC was prevented by NHEb whereas it was not by IP. Furthermore, IP protection and not that obtained by NHEb is abolished by PKC.

Protective effect of nifedipine on myocardial stunning in isolated rabbit hearts: role of high energy phosphates stores.

The aim of the present study was to evaluate the effects of a single dose of nifedipine on myocardial stunning in isolated rabbit hearts. Hearts from rabbits pretreated with a single dose of 20 mg of nifedipine (NIF group) 1-4 h before isolation were compared to control hearts in their response to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. Both experimental groups showed similar baseline cardiac contractility. At the end of the reperfusion period in the control group, isovolumic left ventricular developed pressure (LVDP) and +dP/dtmax had stabilized at 45 +/- 2 and 48 +/- 2% of preischemic values respectively and in the NIF group LVDP stabilized at 63 +/- 6 and +dP/dtmax at 66 +/- 6% (P < 0.05 with respect to the control group). Left ventricular end diastolic pressure (LVEDP) values were significantly lower at the end of reperfusion in the NIF group compared to the controls (36.8 +/- 5.5 mmHg vs 53.4 +/- 3.9 mmHg, P < 0.05). The early impairment of the time constant of relaxation (tau) observed in control hearts was attenuated by pretreatment with nifedipine (control delta tau = 55 +/- 10 ms; NIF group delta tau = 29 +/- 5 ms, P < 0.05). Tissue ATP and creatine phosphate (CP) levels in the control group at the end of reperfusion were 6.9 +/- 0.7 and 8.7 +/- 0.7 mumol/g dry tissue, respectively; in the NIF group ATP and CP levels were significantly higher, 9.2 +/- 0.7 and 11.5 +/- 0.9 mumol/g dry tissue respectively (P < 0.05). Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage during reperfusion were significantly higher in the control group (CK = 120 +/- 15 mU/ml and LDH = 60 +/- 8 mU/ml) compared to the NIF group (CK = 82 +/- 5 mU/ml and LDH = 41 +/- 2 mU/ml, P < 0.05). Our results demonstrate that pretreatment with a single oral dose (20 mg) of nifedipine attenuates systolic and diastolic functional alterations as well as the metabolic impairment associated with stunning in the isolated rabbit heart.

[Post-ischemic myocardial protection with Cabernet-Sauvignon red wine]. / Protección de la función miocárdica post-isquemia por el vino tinto Cabernet-Sauvignon Argentino.

The objective was to assess the action of two Argentine (from Mendoza) non-alcoholic red wine extracts (Cabernet-Sauvignon (CS) and a generic control (G)) on myocardial stunning that follows the reperfusion period. In the isolated isovolumically perfused rat heart the recovery of systolic and diastolic functions after 20 min of global ischemia were assessed through left ventricular developed pressure (LVDP) and end diastolic pressure (EDP), respectively. After 30 min of reperfusion LVDP recovered to 66 +/- 7% in control ischemic hearts. The administration of non-alcoholic extract of CS not of G wine significantly increased the post-ischemic recovery (101 +/- 4%, p < 0.05) of the hearts. The ischemic contracture was not modified by either of the wines. However, during reperfusion the CS, not the G wine, decreased significantly the increase in EDP observed in control ischemic hearts. These results present experimental evidence that the non-alcoholic extracts of CS and not of G Argentine red wine induces protection of postischemic myocardial function.

[The Na+/Ca2+ exchanger as responsible for myocardial stunning]. / El intercambiador Na+/Ca2+ como responsable del atontamiento miocárdico.

Our objective was to assess the participation of Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX) on systolic and diastolic alterations of myocardial stunning. Isolated perfused rat hearts were submitted to 20 min of global ischemia (Is) followed by 30 min of reperfusion (R). This protocol was repeated after treatment before ischemia and/or early in R. with HOE 642 1 microM, a specific blocker of NHE-1 and KB-R7943 1 microM the novel inhibitor of the reverse mode of NCX. In control ischemic hearts the contractility assessed through +dP/dtmax recovered approximately 60%. When the NHE blockade was performed before is or early in R the postischemic recovery reached 100%. The blockade of the reverse mode of NCX only improved significantly the recovery when administered before is and early in R (95 +/- 7%). The ischemic contracture decreased when the treatment with both blockers was performed before Is. During R the increase of end diastolic pressure (EDP) observed in control ischemic hearts (at 30 min of R, EDP value was 44 +/- 4 mmHg) diminished significantly by NHE (24 +/- 6 and 12 +/- 2 mmHg when the blocker was administered before or after Is) and NCX blockade performed before and after is (12 +/- 6 mmHg). These results indicate that the activation of the reverse mode of NCX secondary to the NHE activation during ischemia and reperfusion is the mechanism responsible for the Ca2+ overload involved in the diminution of contractility that characterizes myocardial stunning.

[Effect of nifedipine on cardiac chronotropism in conscious dogs]. / Acción de la nifedipina sobre el cronotropismo cardíaco en perros conscientes.

The effect of nifedipine (NIF) was studied in intact conscious dogs with and without autonomic blockade. Maximal decrease of systolic arterial pressure (delta P, in mmHg), maximal increase of heart rate (delta F, in beats/min), the ratio delta F/delta P, and the time elapsed between delta F and delta P (delta t) were measured after the acute administration of the drug. Two intravenous doses of NIF (50 and 150 micrograms/kg) were administered either alone or after sympathetic and parasympathetic blockade. Group Ia: 50 micrograms/kg of NIF alone. The delta F/delta P and delta T were 3.8 +/- 0.4 and 11.3 +/- 2.2 sec respectively. Group Ib: 150 micrograms/kg of NIF alone. The delta F/delta P and delta T were 2.4 +/- 0.2 and 15 +/- 3 sec respectively. Group IIa: 2 mg/kg of propranolol + 150 micrograms/kg of NIF. The delta F/delta P and delta T were 0.84 +/- 0.4 and 16 +/- 5 sec respectively. Group IIIa: 0.2 mg/kg of atropine + 2 mg/kg of propranolol + 50 micrograms/kg of NIF. In this group left systolic ventricular pressure decreased about 14 mmHg, but the heart rate (HR) was not modified. Group IIIb: 0.2 mg/kg of atropine + 2 mg/kg of propranolol + 150 micrograms/kg of NIF. In this group, left systolic ventricular pressure decreased about 18 mmHg but the HR was not modified. We conclude that acute administration of NIF decreases systolic ventricular pressure and increases HR. The reflex tachycardia is partially abolished by 2 mg/kg of propranolol, and completely abolished by sympathetic and parasympathetic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociation between myocardial relaxation and diastolic stiffness in the stunned heart: its prevention by ischemic preconditioning.

The effects of myocardial stunning and ischemic preconditioning on left-ventricular developed pressure and end-diastolic pressure (diastolic stiffness) as well as on coronary-perfusion pressure were examined in isolated isovolumic rabbit hearts. The isovolumic relaxation was evaluated, and the time constant of pressure decay during the isovolumic period was calculated. Our experimental protocol comprised: 1) myocardial stunning-global ischemia (15 min) followed by reperfusion (30 min); 2) myocardial stunning-global ischemia (20 min) followed by reperfusion (30 min); and 3) ischemic preconditioning--a single cycle of brief global ischemia and reperfusion (5 min each), before a second ischemic period, of 20-min duration. There was no effect upon systolic and diastolic parameters when 15 and 20 minutes of ischemia were evaluated. In both stunned groups the left ventricular developed pressure first recovered to near control values, but then stabilized at only 60% of the control values. Whereas the isovolumic relaxation time constant was increased after 5 min of reperfusion, and return to control values at late reperfusion, the end diastolic pressure remained elevated during the entire period. Values of dP/dV calculated at common pressure levels, were used as a second index of diastolic stiffness. They were increased after stunning, as also was the coronary perfusion pressure. When the heart was preconditioned with a single episode of ischemia, the systolic and diastolic alterations were completely abolished. We thus concluded that diastolic abnormalities incurred by myocardial stunning consist in both an increase in diastolic stiffness and an early impairment of isovolumic relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative cardiovascular effects of nifedipine in anesthetized dogs]. / Acciones cardiovasculares comparativas de la nifedipina en perros anestesiados.

"In vitro" experiments in our laboratory, using coronary conductance arteries, showed that nifedipine produced selective relaxant action. The aim of the present experiments was to demonstrate if this selective vasodilating effect was also detected on coronary resistance vessels of the whole animal. The experiments were performed in anesthetized dogs. In one of the groups a dose-response curve to nifedipine was obtained. In the other group a single dose was infused to each dog. The doses used were: 0.5, 1, 5 and 10 micrograms x kg-1 x min-1. The following parameters were measured: systolic, diastolic (DAP) and mean arterial pressure (MAP); systolic, diastolic (DCF), and mean coronary blood flow; developed tension (DT), heart rate (HR) and cardiac output (CO). Diastolic coronary resistance (DCR) was calculated as the ratio of DAP and DCF. Systemic resistance (SR) was calculated as the ratio of MAP and CO. DAP, MAP, DT and HR remained unchanged with the lowest doses used (0.5 and 1 micrograms x kg-1 x min-1). DCF increased 28 +/- 7% (P less than 0.05) with 0.5 microgram x kg-1 x min-1 and 49 +/- 11% (P less than 0.05) with 1 microgram x kg-1 x min-1. CO increased 13 +/- 3% (P less than 0.05) and 20 +/- 6% (P less than 0.05) respectively. DCR decreased 31 +/- 4% (P less than 0.05) with 0.5 microgram x kg-1 x min-1 and 36 +/- 6% (P less than 0.05) with 1 microgram x kg-1 x min-1. SR decreased 19.5 +/- 5% (P less than 0.05) and 19 +/- 7% (P less than 0.05) respectively. With 5 micrograms x kg-1 x min-1 DAP, MAP and DT decreased 31 +/- 2% (P less than 0.05), 26 +/- 4% (P less than 0.05), and 15 +/- 4% (P less than 0.05) respectively. HR remained unchanged. DCF and CO increased 39 +/- 13% (P less than 0.05) and 35 +/- 11% (P less than 0.05) respectively. DCR and SR decreased 49 +/- 5% (P less than 0.05) and 43 +/- 5% (P less than 0.05) respectively. DAP, MAP and DT decreased 34 +/- 3% (P less than 0.05), 29 +/- 1% and 31 +/- 5% (P less than 0.05) respectively, with 10 micrograms x kg-1 x min-1. HR decreased 9 +/- 3% (P less than 0.05). DCF and CO remained unchanged. DCR and SR decreased 47 +/- 9% (P less than 0.05) and 36 +/- 6% (P less than 0.05) respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Biphasic changes in relaxation following reperfusion after myocardial ischemia.

The present study provides evidences of left ventricular diastolic alterations following reperfusion in a model of global ischemia. Isolated perfused rabbit and rat hearts, were subjected to ischemia for 15 and 20 min respectively, followed by 30 min of reperfusion. In rabbit heart at the end of the reperfusion period, isovolumic left ventricular developed pressure (LVDP) and +dP/dtmax stabilized at 55 +/- 3% and 60 +/- 2% of preischemic values respectively and, in rat heart LVDP = 61 +/- 8% and +dP/dtmax = 57 +/- 9% of preischemic values. Stunned heart was then obtained from both species. Left ventricular end diastolic pressure (LVEDP) values stabilized at the end of reperfusion period at values higher than preischemic conditions in both species (38.9 +/- 4.4 mmHg and 30.3 +/- 3.1 mmHg in rabbit and rat respectively). The time constant of relaxation (T) increased early in reperfusion in both species, but then decreased and stabilized at the end of reperfusion period at values lower than preischemic values. The ratio between both maximal velocities (+P/-P), also showed a transitory impairment in relaxation, followed by normalization and stabilization at values lower than preischemic values. This biphasic pattern in relaxation was detected in both species. The changes in relaxation were dissociated from the diastolic compliance and could be the result of a transitory calcium overload and/or sarcoplasmic reticulum dysfunction. The faster myocardial relaxation at the end of reperfusion period is consistent with the decreased myofilament sensitivity, which characterizes the stunned myocardium.

Adenosine and dipyridamole mimic the effects of ischemic preconditioning.

The effects of preconditioning, adenosine and dipyridamole in protecting the systolic and diastolic alterations of myocardial stunning in rabbit hearts were studied. Isovolumic left ventricular developed pressure (LVDP), and end diastolic pressure (LVEDP) were measured. The time constant of relaxation (T) was calculated. Isolated rabbit hearts were subject to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. LVDP and LVEDP stabilized to 55 +/- 5% and 320 +/- 28% of control values respectively (stunned group) T increased early in reperfusion (from 48.2 +/- 3.9 to 97.2 +/- 10 ms P < 0.05) but returned to control value late in reperfusion. When hearts were preconditioned by a single cycle of 5 min of ischemia LVDP and LVEDP stabilized at 89 +/- 3% and 162 +/- 34% of preischemic values respectively (P < 0.05 with respect to stunned group). The change in T was attenuated (62 +/- 6 ms at 5 min of reperfusion, P < 0.05 with respect to stunned group). Hearts treated either with adenosine (800 micrograms/min) or the nucleoside transport blocker dipyridamole (4 micrograms/min) previously to the ischemia, recovered their LVDP to 86 +/- 1% and 82 +/- 3% of preischemic values, respectively (P < 0.05 with respect to stunned group). Adenosine and dipyridamole also attenuated the increase in LVEDP (195 +/- 12% and 197 +/- 10% respectively, P < 0.05 with respect to stunned group).(ABSTRACT TRUNCATED AT 250 WORDS)

[Substituted sydnonimines: hemodynamic effects and distribution of coronary blood flow in normal and ischemic myocardium]. / Sidnoniminas substituidas: efectos hemodinámicos y distribución de flujo coronario en miocardio normal e isquemico.

Some aspects of hemodynamic effects and distribution of coronary flow of molsidomine were evaluated in anesthetized dogs with open chest. Three experimental groups were performed: In groups I and II 100 micrograms/kg and 200 micrograms/kg of molsidomine were administered respectively. Cardiac output (CO), end diastolic pressure (EDP), mean arterial pressure (MAP), heart rate (HR), systolic left ventricular pressure (SLVP), their maximal rates of development and fall (+P and -P, respectively), developed tension (DT), their maximal contraction (+T) and relaxation (-T) rates, were measured. Peripheral resistance (PR) and the ratios +P/-P and +T/-T were calculated. In group III 100 micrograms/kg of molsidomine were administered after the ligature of the anterior descendent artery (AD) was performed. In this group the distribution of coronary flow was measured through radioactive microspheres injection in the circumflex area (CX) (normal area) and in the AD area (ischemic area). After injecting the microspheres and following its effects for one hour, the maximum effect was determined in 30 minutes. Heart rate did not show any statistically significant variation at any of the doses used. MAP fell from 92 +/- 3 mmHg to 77 +/- 5 mmHg (P less than 0.05) in group I and from 87 +/- 3 mmHg to 69 +/- 4 mmHg in group II. Cardiac output fell from 1.63 +/- 0.13 1/min to 1.22 +/- 0.12 1/min (P less than 0.05) in group I and from 1.60 +/- 0.19 1/min to 1.13 +/- 0.18 1/min (P less than 0.05) in group II. PR did not show any significant change in any of the groups. +P decreased 13 +/- 6% (P less than 0.05) in group I and 13 +/- 5% (P less than 0.05) in group II. The decrease of -P was of 17 +/- 5% (P less than 0.05) in both groups. EDP decreased from 6.0 +/- 1.0 mmHg to 3.9 +/- 0.9 mmHg (P less than 0.05) and from 5.5 +/- 0.5 mmHg to 2.9 +/- 0.8 mmHg (P less than 0.05) in groups I and II, respectively. DT, +T, -T, +T/-T and +P/-P did not show any significant change. EDP fell from 8 +/- 1 mmHg to 4.1 +/- 1.3 mmHg (P less than 0.05); MAP fell from 82 +/- 4 mmHg to 62 +/- 6 mmHg (P less than 0.05) and CO fell from 2.05 +/- 0.27 1/min to 1.30 +/- 0.14 1/min in group III. HR and PR did not show any significant change in group III.(ABSTRACT TRUNCATED AT 400 WORDS)

[Hemodynamic effects of changes in the heart rate]. / Efectos hemodinámicos de los cambios de la frecuencia cardíaca.

The effects of the variations in heart rate (HR) within the range of 80 and 180 beats/min were studied in open-chest dogs with complete AV block. Left ventricular systolic pressure (LVSP) and the maximal velocities of development (+P) and fall (-P), left ventricular end diastolic pressure (LVEDP), cardiac output (CO) and duration of ejection (DE) were recorded and analyzed. Contractility was assessed by the force developed by an isometric segment of the left ventricular wall (DT) and the maximal velocities of rise (+T) and fall (-T). Stroke volume (SV), stroke work (SW), stroke power (SP), +P/-P and +T/-T ratios, the time constant of LV pressure fall during isovolumic relaxation (T tau), and mean rate of ejection of left ventricle (MRE) were calculated from the precedent data. LVSP, LVEDP and -P did not show any statistically significant difference, while +P fell by 10 +/- 5% and 16 +/- 4% at 160 and 180 beats/min, respectively. +P/-P ratios were 1.25 +/- 0.07 at 80 beats/min; 1.08 +/- 0.06 at 140 beats/min (P less than 0.01); 1.03 +/- 0.05 at 160 beats/min (P less than 0.01) and 1.02 +/- 0.06 at 180 beats/min (P less than 0.01). CO remained unchanged and due to this SV fell significantly when HR increased. DT, +T, -T, +T/-T and T (tau) were unchanged. DE fell significantly at 120, 140, 160 and 180 beats/min with respect to the initial HR. SW fell significantly at every HR studied. MRE was 147 +/- 13 ml/sec at 80 beats/min and 100 +/- 8 and 93 +/- 7 ml/sec at 160 and 180 beats/min, respectively (P less than 0.01 with respect to control). SP was 161.7 +/- 19.3 g X m X sec-1 at 80 beats/min, and 122.3 +/- 13.2 and 103.8 +/- 9.2 g X m X sec-1 at 160 and 180 beats/min, respectively (P less than 0.01 with respect to control). We may come to the following conclusions: 1) When HR changed in our experimental conditions, CO remained unchanged and due to this the SV fell significantly, showing the difficulty of the heart pump to regulate the CO by itself. 2) The process of relaxation is not affected within the used HR range. 3) In our experiments the inotropic effect due to increments of heart rate ("Bowditch staircase phenomenon") was not detected. However, it might become evident in preparations with more depressed contractility.

The effects of Bay K 8644 on diastolic function in the dog heart.

The effects of increased cytosolic calcium on cardiac mechanics were studied in open chest dogs instrumented with ultrasonic crystals and a miniature pressure transducer. Calcium was increased either by promoting calcium influx with Bay K 8644 (Bay K) or by increasing extracellular calcium concentration. A single dose of Bay K (10 micrograms/kg/min) was administered to each dog. Bay K increased LV systolic pressure, maximal rate of rise of LV pressure (LV + dP/dt), mean velocity of circumferential fiber shortening (Vcf), and calculated LV end-systolic wall stress. The time constant of isovolumic pressure decay (T) was calculated following two different methods: (a) a semilogarithmic method (Tz), and (b) using the linear relation between LV - dP/dt vs LV pressure (T1). Whereas Tz decreased from 31.7 +/- 2.6 to 26.7 +/- 1.7 ms (P less than 0.05), no changes were detected in T1 (46.3 +/- 4.4 vs 50.9 +/- 4.0 ms N.S.) The asymptote value (PB) decreased after Bay K from -9 +/- 2.8 to -22.5 +/- 4.2 mmHg (P less than 0.05). The same results were obtained when the changes in the loading conditions of the heart produced by Bay K were controlled by mechanical manoeuvers or after beta-blockade with propranolol. When calcium chloride was administered in amounts that will produce equal contractile changes as Bay K, a decrease in PB was also observed (from -14.7 +/- 1.6 to -27.7 +/- 6.1 mmHg (P less than 0.05]. Tz decreased from 29.6 +/- 3.6 to 22.5 +/- 2.9 ms (P less than 0.05) and no changes in T1 (52.5 +/- 5 vs 52.4 +/- 7.3 ms, N.S.) were detected. The decrease in the asymptote reported herein could induce a false decrease in the time constant if the altered values of PB are not considered, or another method of calculation of the time constant is used. Neither Bay K nor elevated extracellular calcium concentration modified the diastolic compliance. Changes in loading conditions or a cAMP pathway can be ruled out as a cause of the decrease in PB, since the results were reproduced under controlled loading conditions and beta blockade. These data suggest that increasing cytosolic calcium does not alter either the relaxation rate or the diastolic compliance but does decrease the value toward left ventricular pressure decays.