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At least 19 recordsLinked to original sources
PubMed1982

The effect of dopamine on postburn myocardial depression.

Myocardial performance is severely depressed following burns to more than 30% of the body surface area. Cardiac output in the immediate postburn period is dissociated from plasma volume. Many attempts have been made to improve early postburn hemodynamics with little success. Continuous infusion dopamine in low doses has recently been reported to improve at least one index of cardiac performance (LVSWI). We report the use of low-dose (5-10 mcg/kg X min) dopamine in the first 24 hours postburn in 20 seriously burned adults. Hemodynamic data are presented immediately preinfusion and after 1 hour of dopamine. Low-dose dopamine produced no change in cardiac index, arterial pressure, LVSWI, or any other hemodynamic parameter. We conclude that dopamine is of no benefit in treating the depressed myocardial function seen following major burns.

Adult↗
PubMed1996

Endotoxin induces cardiac HSP70 and resistance to endotoxemic myocardial depression in rats.

Endotoxin (bacterial lipopolysaccharide, LPS) depresses myocardial function. However, heat shock and sublethal LPS can confer cardiac resistance to postischemic dysfunction. We hypothesized that a prior exposure to LPS stress induces the expression of cardiac heat shock protein 70 (HSP70) and resistance to endotoxemic myocardial depression. Moreover, induction of HSP70 by hyperthermia should also increase cardiac resistance to LPS toxicity. LPS (500 micrograms/kg ip) depressed rat left ventricular developed pressure (LVDP) maximally at 6 h (58.4 +/- 3.72 vs. 101 +/- 1.46 mmHg in saline control, P < 0.01), and myocardial contractile function recovered at 24 h. In rats pretreated with LPS 24 h earlier, subsequent LPS exposure did not depress LVDP (97.0 +/- 3.53 mmHg at 6 h, P < 0.01 vs. single exposure). Both LPS and hyperthermia (42 degrees C, 15 min) induced HSP72 mainly in the cardiac interstitial cells, including macrophages at 24 h after treatment. When hyperthermia-pretreated animals were similarly challenged with LPS, myocardial depression at 6 h was partially abrogated (LVDP 80.1 +/- 5.67 vs. 62.2 +/- 4.91 mmHg in sham+LPS group, P < 0.01). We conclude that LPS induces HSP70 in rat heart and that an exposure to LPS or heat stress confers cardiac resistance to endotoxemic myocardial depression.

Animals↗
PubMed1992

Additive myocardial depressant effects of cocaine and ethanol.

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.

Animals↗
PubMed1985

A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance.

We have previously described a subpopulation of patients with septic shock who had a reversible depression of radionuclide-determined left ventricular ejection fraction (EF). To investigate the mechanism of this myocardial depression, an in vitro model of mammalian myocardial cell performance was established employing primary spontaneously beating rat myocardial cells. The contraction of a single cardiac cell was quantitated by recording the changes in area occupied by the cell during contraction and relaxation. In 20 septic shock patients during the acute phase, the mean left ventricular EF was decreased (mean = 0.33, normal mean = 0.50), and serum obtained during this acute phase induced a mean (+/- standard error of the mean) 33 +/- 4% decrease in extent and 25 +/- 4% decrease in velocity of myocardial cell shortening during contraction (P less than 0.001). In contrast, serum obtained from 11 of these same patients before shock (n = 2) or after recovery (n = 9) of the left ventricular EF (mean = 0.50) showed a return toward normal in extent and velocity of shortening (P less than 0.001). Sera from 17 critically ill nonseptic patients, from 10 patients with structural heart disease as a cause for a depressed EF, and from 12 healthy laboratory personnel, induced no significant changes in in vitro myocardial cell performance. In 20 patients during the acute phase of septic shock, the decreased EF in vivo demonstrated a significant correlation (r = +0.52, P less than 0.01) with a decrease in the extent of myocardial cell shortening in vitro. The quantitative and temporal correlation between the decreased left ventricular EF and this serum myocardial depressant substance argues for a pathophysiologic role for this depressant substance in producing the reversible cardiomyopathy seen during septic shock in humans.

Adolescent↗
PubMed1995

Myocardial depression by isoflurane is dependent on the underlying beta-adrenergic tone.

Depression of myocardial contractility by muscarinic agonists is dependent on underlying beta-adrenergic tone. The negative inotropic effect of muscarinic agonists is enhanced by previous beta-adrenergic stimulation, an action that has been termed accentuated antagonism. We wished to determine whether accentuated antagonism occurs with isoflurane-induced myocardial depression. We used an isolated, electrically stimulated rat left atrium model to compare the dose-response curves to the muscarinic agonist carbachol and isoflurane under conditions of high (10(-6)M isoproterenol added to the bath) or low (10(-6)M propranolol) beta-adrenergic tone. As expected, myocardial depression by carbachol was accentuated in preparations stimulated with isoproterenol as compared with atria treated with propranolol. The decrease in contractility induced by isoflurane was attenuated in isoproterenol-stimulated preparations as compared with beta-blocked atria. The increased sensitivity to isoflurane observed in propranolol-treated muscles was reversed by increasing the concentration of calcium in the bath from 2.5 to 5.0 mM. In contrast to muscarinic agonists, isoflurane-induced myocardial depression is attenuated by previous beta-adrenergic stimulation. Isoproterenol most likely attenuates isoflurane's negative inotropic action by increasing the availability of external calcium. The results of this study demonstrate that the underlying beta-adrenergic tone greatly influences the negative inotropic response of cardiac tissue of isoflurane.

Anesthetics, Inhalation↗
PubMed1996

In vitro myocardial depression by ketamine or thiopental is dependent on the underlying beta-adrenergic tone.

BACKGROUND: Depression of myocardial contractility by muscarinic stimulation is dependent on the underlying beta-adrenergic tone. Prior beta-adrenergic stimulation enhances muscarinic negative inotropic responses, an effect that has been termed accentuated antagonism. The purpose of this study was to determine whether accentuated antagonism occurs with myocardial depression caused by thiopental or ketamine. METHODS: Using an isolated, electrically stimulated rat left afrium model, the dose-response curves to the muscarinic agonist carbachol and the anesthetics ketamine and thiopental were compared under conditions of high (10(-6)M isoproterenol bath concentration) or low (10(-6)M propranolol) beta-adrenergic tone. RESULTS: As expected, depression by carbachol was accentuated in preparations stimulated with isoproterenol compared with atria treated with propranolol. The decrease in tension by high doses (> 400 muM thiopental, > 200 muM ketamine) of thiopental or ketamine was attenuated in isoproterenol-stimulated tissue when compared with beta-adrenergic blocked muscle. Low concentrations (200 muM thiopental, 100 muM ketamine) of anesthetic caused either no change in contractility (thiopental) or small positive inotropic responses (ketamine) in pro-pranolol-treated but not isoproterenol-stimulated tissue. CONCLUSIONS. In contrast to muscarinic agonists, myocardial depression by high concentrations of ketamine or thiopental is attenuated by prior beta-adrenergic stimulation. Positive inotropic responses may be seen with low concentrations of ketamine in muscle with low beta-adrenergic tone. The results of this study demonstrate that the underlying beta-adrenergic tone greatly influences the in vitro response of cardiac tissue to ketamine or thiopental.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression.

The effect of myocardial depression on the circulatory response to acute normovolemic hemodilution (hematocrit 23%) with hetastarch was evaluated in 28 anesthetized Sprague-Dawley rats. Cardiac output was recorded using an electromagnetic flow probe. Mild, moderate, and severe myocardial depression were achieved by infusing disopyramide 50, 75, and 85 mg/kg. This resulted in a dose-dependent decrease in cardiac output (r = -0.73, p less than 0.05) and mean arterial pressure (r = -0.65, p less than 0.05), and an increase in left ventricular end-diastolic pressure (r = 0.77, p less than 0.05) and total peripheral resistance (r = 0.46, p less than 0.05). Following hemodilution, cardiac output and mean arterial pressure were significantly lower and total peripheral resistance significantly higher in animals with myocardial depression compared with saline anemic controls. These differences were dose-dependent for cardiac output (r = -0.83, p less than 0.05), mean arterial pressure (r = -0.68, p less than 0.05), and total peripheral resistance (r = 0.51, p less than 0.05). Although control animals were able to significantly increase their cardiac output and stroke volume after hemodilution compared with baseline, animals with severe myocardial depression were unable to do so. This resulted in marked hypotension after hemodilution in controls compared with severely depressed animals. The results suggest a diminished ability of the pharmacologically depressed heart to tolerate acute normovolemic hemodilution.

Animals↗
PubMed2002

Characterization of a myocardial depressant factor in meningococcal septicemia.

OBJECTIVE: Identification and characterization of myocardial depressant factors present in meningococcal septicemia. DESIGN: Laboratory investigation of myocardial depression that used isolated cardiac myocytes as an model of cardiac contractile function. SETTING: University hospital and laboratories. PATIENTS: Children with severe meningococcal septic shock requiring intensive care. ANIMALS: Myocytes obtained from adult male Sprague-Dawley rats. INTERVENTIONS: Serum samples obtained from the acute phase of sepsis were evaluated for the presence of myocardial depressant activity. Further characterization of the myocardial depressant factor was undertaken by using cell culture supernatants from whole blood and peripheral blood mononuclear cells that had been exposed to heat-killed meningococci. MEASUREMENTS AND MAIN RESULTS: Myocardial depressant activity was measured by using isolated rat left-ventricular myocytes. Changes in amplitude of contraction and in the speed of contraction and relaxation were determined after cells were exposed to various stimuli. Serum from patients with meningococcal disease had myocardial depressant activity. This activity was also present in whole blood and peripheral blood mononuclear cells exposed to meningococci. Myocardial depressant activity was found to be heat stable, proteinaceous, and of a molecular weight range of 10-25 kDa. The activity did not elevate concentrations of cyclic guanylic acid. Lipopolysaccharide-binding protein augmented the release of myocardial depressant factor by peripheral blood mononuclear cells exposed to meningococci. CONCLUSIONS: Myocardial depression in meningococcal sepsis is mediated in part by circulating myocardial depressant factors. Myocardial depressant factors are also released when whole blood or peripheral blood mononuclear cells of healthy donors are exposed to heat-killed meningococci. Release of the factors appears to be mediated through endotoxin-induced activation of peripheral blood mononuclear cells, since lipopolysaccharide-binding protein augments release in a dose-responsive manner. Partial physicochemical characterization of the factors has been achieved.

Adolescent↗
PubMed2003

Acute reversible myocardial depression associated with sepsis.

A 30-year-old man was admitted to our hospital for left lobar pneumonia with septic shock. Acute left-sided heart failure became evident as sepsis developed. Echocardiography revealed diffuse severe hypokinesis of the left ventricle (LV) and a pulmonary artery catheter showed Forrester subset II hemodynamics. Along with amelioration of sepsis and decrease of the serum concentrations of tumor necrosis factor-alpha and interleukin-6, LV hypokinesis improved. It is suggested that the patient's heart failure may have been due to functional depression of myocardial contractility resulting from a direct effect of the cytokines towards the cardiomyocytes, the so-called "septic myocardial depression".

Adult↗
PubMed1982

The pathophysiologic role of myocardial depressant factor as a mediator of circulatory shock.

Myocardial Depressant Factor (MDF) is a small peptide circulating in the blood of all mammalian species tested in a variety of shock states including endotoxic, hemorrhagic, cardiogenic, bowel ischemic, acute pancreatitis, burn, and traumatic shock. MDF is produced by the action of proteolytic enzymes released by the ischemic pancreas. MDF acts to depress myocardial contractility, constrict the splanchnic arteries and impair reticuloendothelial system phagocytosis. Several pharmacologic agents prevent the formation of MDF including membrane stabilizers (e.g., glucocorticoids), protease inhibitors (e.g., aprotinin), converting enzyme inhibitors (e.g., captopril), prostaglandins (e.g., PGE1 and PGI2), thromboxane synthetase inhibitors (e.g., imidazole, PTA2) and local anesthetics (e.g., lidocaine). Prevention of MDF formation or action improves survival. Thus, MDF is an important mediator of shock pathophysiology and should be considered in the therapy of circulatory shock states.

Animals↗
PubMed1978

Myocardial depression in sepsis.

Myocardial failure is uniformly fatal when associated with post-traumatic sepsis and multisystem failure. Controversy exists as to whether endotoxin has a direct effect on the myocardium. A nonanoxic isolated arterially perfused rabbit interventricular septum was used in this study to evaluate the effects of endotoxin, live E. coli, and endotoxin/septic shock plasma on myocardial function and ultrastructure. Purified E. coli endotoxin and live E. coli bacteria did not have a significant direct effect on rabbit cardiac muscle function or ultrastructure. Perfusion of the rabbit septum with plasma from rabbits exsanguinated following a 2-hour septic or endotoxin shock insult, however, caused significant (p less than 0.02) myocardial depression when compared with control septa perfused with normal rabbit plasma. Septa perfused with shock plasma demonstrated ultrastructural alterations of mitochondria that were not noted in control preparations.

Animals↗
PubMed1998

Depressed myofilament co-operativity associated with post-cardioplegic myocardial depression.

The mechanism underlying myocardial depression after procedures involving cardioplegia are unknown. We tested the hypothesis that such depression was associated with altered myofilament interactions, using isolated hearts perfused with warm (37 degreesC), oxygenated (95% O2/5% CO2) Krebs-Ringer's bicarbonate (KRB) buffer. A latex balloon was inserted into the left ventricle (LV) to monitor LV function. All hearts underwent a 30-min equilibration period. One group of hearts (CPL+RPR) were arrested with St Thomas #2 cardioplegic solution (4 degreesC; 3 ml followed by 1 ml every 15 min) for 120 min, followed by reperfusion with warm, oxygenated KRB. A second group underwent cardioplegic arrest with no reperfusion (CPL). A third group underwent 60 min of warm, oxygenated perfusion with KRB beyond the equilibration period (60 MIN). The last group only underwent the equilibration period (EQUIL). LV function was assessed at the end of equilibration, and at 30 and 60 min of reperfusion (or 30 and 60 min additional perfusion in the 60 MIN group). All hearts were frozen at the end of the temporal protocol for each group, and stored at -70 degreesC for later measurement of Ca2+-stimulated Mg2+ ATPase activity after isolation of myofibrils. CPL+RPR hearts demonstrated significant depression of systolic pressure and elevation diastolic pressure at fixed volumes, compared to baseline and 60 MIN group values. There were no significant changes in the amount of constituent myofilament proteins, as assessed by densinometric analyses of Western blots. There were also no changes in the minimal or maximal ATPase activities, nor in the pCa50, indicating no effect of cardioplegic arrest on myofilament sensitivity to calcium. However, all hearts that underwent cardioplegic arrest were found to have significantly lower Hill coefficients (1.85+/-0.09 and 1.85+/-0.13 v 2.31+/-0.13 and 2.34+/-0. 14 in CPL+RPR and CPL v 60 MIN and EQUIL hearts, respectively), suggesting decreased co-operativity of the actomyosin interaction. Such a decrease in co-operativity would contribute to both the systolic and diastolic alterations associated with myocardial depression after cardioplegic arrest. These changes were associated with the cardioplegic event, and appeared to be independent of reperfusion.

Actin Cytoskeleton↗
PubMed2001

Biosynthesis of constitutive nitric oxide synthase-derived nitric oxide attenuates coronary vasoconstriction and myocardial depression in a model of septic heart failure induced by Staphylococcus aureus alpha-toxin.

OBJECTIVE: Myocardial depression, which frequently occurs in the course of septic shock, has been attributed to the cardiodepressant properties of nitric oxide (NO) generated by either the inducible NO synthase (iNOS) or the constitutive isoform (cNOS). We have previously demonstrated that alpha-toxin from Staphylococcus aureus induces thromboxane-mediated vasoconstriction accompanied by severe cardiodepression in isolated rat hearts. In the present study, we investigated the role of NO in the alpha-toxin-induced vascular and contractile abnormalities. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Isolated hearts from male Wistar rats. INTERVENTIONS: Isolated hearts were perfused with purified staphylococcal alpha-toxin for 60 mins. MEASUREMENTS AND MAIN RESULTS: At a concentration of 0.25 and 0.5 microg/mL, alpha-toxin induced a rise in coronary perfusion pressure, depressed myocardial contractility, and caused edema formation. Simultaneously, a time- and dose-dependent rapid release of NO into the perfusate was noted as quantified by a chemiluminescence technique. L-NMMA, a nonselective inhibitor of NOS, but not PBITU, an iNOS-selective inhibitor, blocked NO synthesis, markedly increased the rise in coronary perfusion pressure and the loss in contractility, and enhanced edema formation in response to alpha-toxin. In contrast, zaprinast, a selective inhibitor of phosphodiesterase type V that is used for stabilization of cyclic guanosine monophosphate, attenuated the toxin-induced coronary vasoconstrictor response and the myocardial depression. L-arginine, the substrate of NOS, had similar, yet less potent, effects as zaprinast and slightly increased the release of NO caused by alpha-toxin. Immunohistochemical analysis of the myocardium at the end of the perfusion period demonstrated a positive staining for cNOS but not for iNOS. In addition, no up-regulation of iNOS mRNA was detected in the tissue of toxin-exposed hearts. CONCLUSIONS: Staphylococcal alpha-toxin provokes NO biosynthesis via activation of cNOS in rat hearts. NO partly antagonizes the deleterious effects of this pathogenicity factor on coronary vasoregulation and myocardial performance.

Animals↗
PubMed2004

N,N',N"-triacetylglucosamine, an inhibitor of lysozyme, prevents myocardial depression in Escherichia coli sepsis in dogs.

OBJECTIVE: Reversible myocardial depression in sepsis has been ascribed to the release of inflammatory mediators. We recently found that lysozyme c (Lzm-S), consistent with that originating from the spleen, was a mediator of myocardial depression in an Escherichia coli model of septic shock in dogs. We further showed in a right ventricular trabecular (RVT) preparation that Lzm-S's depressant activity could be blocked by N,N',N" triacetylglucosamine (TAC), a competitive inhibitor of Lzm-S. We hypothesized that Lzm-S binds to or cleaves a cardiac membrane glycoprotein, thereby interfering with myocardial contraction in sepsis. In the present study, we examined whether TAC could prevent myocardial depression in an in vivo preparation and whether other related N-acetylglucosamine (NAG) structures could also inhibit Lzm-S's effect in RVT. DESIGN: Randomized experimental study. SETTING: University laboratory. SUBJECTS: Anesthetized, mechanically ventilated dogs. INTERVENTIONS: We produced sepsis by infusion of E. coli over an approximately 6-hr period. MEASUREMENTS AND MAIN RESULTS: We examined the effect of TAC on stroke work, our primary index of myocardial function, when treatment was administered before sepsis (pretreatment) and after 1.5 hrs (early treatment study) and 3.5 hrs of sepsis (late treatment study; LTS). In the pretreatment study and early treatment study, myocardial depression would have not yet occurred but would have already been present in the late treatment study. In RVT, we assessed the effect of other NAG oligosaccharides and variants to the NAG structure on Lzm-S's depressant activity. In pretreatment and the early treatment study, TAC prevented the reduction in stroke work observed in nontreated septic groups but did not reverse the reduction found in the late treatment study. In RVT, of the compounds tested, only N,N'-diacetylglucosamine showed an inhibitory effect. CONCLUSIONS: We found that TAC, a competitive inhibitor of Lzm-S, prevented myocardial depression in experimental sepsis. Only specific NAG structures are inhibitory to Lzm-S's depressant activity. TAC may be useful in attenuating cardiovascular collapse in sepsis.

Acetylglucosaminidase↗
PubMed1998

TNF-alpha and myocardial depression in endotoxemic rats: temporal discordance of an obligatory relationship.

Exogenous tumor necrosis factor-alpha (TNF-alpha) induces delayed myocardial depression in vivo but promotes rapid myocardial depression in vitro. The temporal relationship between endogenous TNF-alpha and endotoxemic myocardial depression is unclear, and the role of TNF-alpha in this myocardial disorder remains controversial. Using a rat model of endotoxemia not complicated by shock, we sought to determine 1) the temporal relationship of changes in circulating and myocardial TNF-alpha with myocardial depression, 2) the influences of protein synthesis inhibition or immunosuppression on TNF-alpha production and myocardial depression, and 3) the influence of neutralization of TNF-alpha on myocardial depression. Rats were treated with lipopolysaccharide (LPS, 0.5 mg/kg ip). Circulating and myocardial TNF-alpha increased at 1 and 2 h, whereas myocardial contractility was depressed at 4 and 6 h. Pretreatment with cycloheximide or dexamethasone abolished the increase in circulating and myocardial TNF-alpha and preserved myocardial contractile function. Similarly, treatment with TNF binding protein immediately after LPS prevented myocardial depression. We conclude that endogenous TNF-alpha mediates delayed myocardial depression in endotoxemic rats and that inhibition of TNF-alpha production or neutralization of TNF-alpha preserves myocardial contractile function in endotoxemia.

Analysis of Variance↗
PubMed2002

Clinical review: Myocardial depression in sepsis and septic shock.

Myocardial dysfunction frequently accompanies severe sepsis and septic shock. Whereas myocardial depression was previously considered a preterminal event, it is now clear that cardiac dysfunction as evidenced by biventricular dilatation and reduced ejection fraction is present in most patients with severe sepsis and septic shock. Myocardial depression exists despite a fluid resuscitation-dependent hyperdynamic state that typically persists in septic shock patients until death or recovery. Cardiac function usually recovers within 7-10 days in survivors. Myocardial dysfunction does not appear to be due to myocardial hypoperfusion but due to circulating depressant factors, including the cytokines tumor necrosis factor alpha and IL-1beta. At a cellular level, reduced myocardial contractility seems to be induced by both nitric oxide-dependent and nitric oxide-independent mechanisms. The present paper reviews both the clinical manifestations and the molecular/cellular mechanisms of sepsis-induced myocardial depression.

Cardiac Output, Low↗
PubMed1997

The direct effects of diazepam and midazolam on myocardial depression in cultured rat ventricular myocytes.

UNLABELLED: We examined the direct myocardial depressant effects of diazepam and midazolam and determined whether a benzodiazepine receptor antagonist, flumazenil, or an L-type Ca2+ channel agonist, Bay K 8644, affects the myocardial depression induced by diazepam and midazolam in cultured rat ventricular myocytes. Ventricular myocytes of neonatal rats were obtained by enzymatic digestion with collagenase and cultured for 6-7 days. The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and amplitude were measured by determining displacement with a fiberoptic sensor. Myocytes were exposed to either diazepam or midazolam at concentrations of 0.1, 1, 10, and 100 microM. The beating rate and amplitude were measured 4 min after diazepam or midazolam administration. In other cells, either diazepam or midazolam was administered at each concentration in the presence of flumazenil or Bay K 8644. Midazolam and diazepam decreased the beating rate and amplitude concentration-dependently. These myocardial depressant effects were prevented by Bay K 8644 and, to a lesser degree, by flumazenil. Thus, the L-type Ca2+ channel is important in the direct myocardial depression caused by diazepam and midazolam. IMPLICATIONS: This study describes the direct effect of midazolam and diazepam on intrinsic myocardial contraction using cultured rat ventricular heart cells. Both of these drugs have a direct myocardial depressant effect at the cellular level, which is mainly mediated by an inhibition of the sarcolemmal L-type Ca2+ channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗