title: Negative inotropic drugs alter indexes of cytosolic [Ca(2+)]-left ventricular pressure relationships after ischemia.
abstract: Negative inotropic agents may differentially modulate indexes of cytosolic [Ca(2+)]-left ventricular (LV) pressure (LVP) relationships when given before and after ischemia. We measured and calculated [Ca(2+)], LVP, velocity ratios [[(d[Ca(2+)]/dt(max))/(dLVP/dt(max)); VR(max)] and [(d[Ca(2+)]/dt(min))/(dLVP/dt(min)); VR(min)]], and area ratio (AR; area [Ca(2+)]/area LVP per beat) before and after global ischemia in guinea pig isolated hearts. Ca(2+) transients were recorded by indo 1-AM fluorescence via a fiberoptic probe placed at the LV free wall. [Ca(2+)]-LVP loops were acquired by plotting LVP as a function of [Ca(2+)] at multiple time points during the cardiac cycle. Hearts were perfused with bimakalim, 2,3-butanedione monoxime (BDM), nifedipine, or lidocaine before and after 30 min of ischemia. Before ischemia, each drug depressed LVP, but only nifedipine decreased both LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. After ischemia, each drug depressed LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. Each drug except BDM decreased d[Ca(2+)]/dt(max); nifedipine decreased d[Ca(2+)]/dt(min), whereas lidocaine increased it, and bimakalim and BDM had no effect on d[Ca(2+)]/dt(min). Each drug except bimakalim increased VR(max) and VR(min) before ischemia; after ischemia, only BDM and nifedipine increased VR(max) and VR(min). Before and after ischemia, BDM and nifedipine increased AR, whereas lidocaine and bimakalim had no effect. At 30 min of reperfusion, control hearts exhibited marked Ca(2+) overload and depressed LVP. In each drug-pretreated group Ca(2+) overload was reduced on reperfusion, but only the group pretreated with nifedipine exhibited both higher LVP and lower [Ca(2+)]. These results show that negative inotropic drugs are less capable of reducing [Ca(2+)] after ischemia so that there is a relatively larger Ca(2+) expenditure for contraction/relaxation after ischemia than before ischemia. Moreover, the differential effects of pretreatment with negative inotropic drugs on [Ca(2+)]-LVP relationships after ischemia suggest that these drugs, especially nifedipine, can elicit cardiac preconditioning.
authors.affiliation: Department of Physiology, The Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Samhita S
authors.initials: SS
authors.lastname: Rhodes
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011312:Pressure; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D004095:Dihydropyridines; C004717:diacetylmonoxime; C061050:bimakalim; D008012:Lidocaine; D009543:Nifedipine; D003931:Diacetyl; D002118:Calcium