How inotropic drugs alter dynamic and static indices of cyclic myoplasmic [Ca2+] to contractility relationships in intact hearts.
The authors examined effects of positive (dopamine and digoxin) and negative (nifedipine and lidocaine) inotropic interventions on the instantaneous cyclic relationship between myoplasmic [Ca2+] and simultaneously developed left ventricular pressure (LVP) in intact guinea pig hearts. Novel indices were developed to quantify this relationship based on (1) transient [Ca2+] and LVP signal morphology, ie, maxima and minima, peak derivatives, beat areas, durations, and ratios of indices of LVP to [Ca2+]; (2) temporal delay; and (3) LVP versus [Ca2+] loop morphology, ie, orientation, size, hysteresis, position, shape, and duration. These analyses were used to assess the cost of phasic [Ca2+] for contraction and relaxation over one beat after inotropic intervention. It was found that dopamine and digoxin increased contractile and relaxation responsiveness to phasic [Ca2+], cumulative Ca2+, and net Ca2+ flux. Unlike dopamine, digoxin did not decrease relaxation response time. Nifedipine and lidocaine decreased contractile and relaxation responsiveness to phasic [Ca2+], cumulative Ca2+, and net Ca2+ flux. Unlike lidocaine, nifedipine decreased net available Ca2+ and Ca2+ influx. Positive inotropic agents increased [Ca2+]-LVP loop area and hysteresis and resulted in a more vertically oriented loop. Nifedipine and lidocaine decreased these loop indices and lidocaine exhibited greater loop hysteresis than did nifedipine. These novel indices provide a quantitative assessment of myoplasmic [Ca2+] handling for cardiac contractile function.
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000502:physiology*; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004298:Dopamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009543:Nifedipine / Q000008:administration & dosage / Q000493:pharmacokinetics; D012815:Signal Processing, Computer-Assisted; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology
D004077:Digoxin; D008012:Lidocaine; D009543:Nifedipine; D002118:Calcium; D004298:Dopamine