Exogenous Calcium Preconditions Myocardium from Patients Taking Oral Sulfonylurea Agents

Cain, Brian S.; Meldrum, Daniel R.; Meng, Xianzhong; Pulido, Edward J.; Shames, Brian D.; Selzman, Craig H.; Banerjee, Anirban; Harken, Alden H.

doi:10.1006/jsre.1999.5718

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…Nif protects when given after I/R injury (12,25,34,35,41), but little is known about a possible preconditioning effect before ischemia. Cain et al (7) conducted in vitro experiments on human atrial trabecular tissue removed from patients receiving Ca 2ϩ channel blockers and found that ischemic preconditioning was prevented; moreover, exogenous CaCl 2 added to the bath elicited preconditioning (8). We found that Nif reduced both cytosolic [Ca 2ϩ ] and LVP before ischemia and preserved [Ca 2ϩ ]-LVP loop characteristics better than the other drugs that reduced LVP but not systolic [Ca 2ϩ ].…”

Section: Discussionmentioning

confidence: 85%

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Camara

Chen²,

Rhodes³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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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.

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Section: Discussionmentioning

confidence: 85%

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Camara

Chen²,

Rhodes³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…1). Thus, KATP channels may be more of a “trigger” than an “effector.” Defining the role of KATP channels in preconditioning is clinically important in that commonly prescribed oral hypoglycemic medications (sulfonylurea agents) 47 inhibit the mitochondrial KATP channel preventing adaptive cardiac preconditioning. This may explain the paradoxical increased cardiovascular risk in diabetic patients controlled with oral agents as compared to presumably sicker diabetics requiring insulin 48 …”

Section: Preconditioning Signalsmentioning

confidence: 99%

Ischemic Preconditioning: Fact or Fantasy?

Raeburn¹,

Zimmerman²,

Arya³

et al. 2002

Journal of Cardiac Surgery

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Fifteen years ago, an experimental effort to magnify a myocardial infarction, with preinfarction episodes of transient ischemia, proved paradoxically protective. In the ensuing years, surgeons have learned to discriminate a biochemical/metabolic/functional spectrum of cardiac states ranging from healthy myocardium to "stunned" or "hibernating" heart to the modes of "apoptotic" or "necrotic" cardiomyocyte death. It is now clear that "protective cardiac preconditioning" influences all of these cardiac states. The cellular mechanisms of preconditioning (PC) are now sufficiently understood to permit clinical application. Ligation of adrenergic, adenosine, bradykinin or opioid receptors involves signaling via both tyrosine and calcium-dependent protein kinases (PKC), which activate mitochondrial ATP-dependent potassium channels. Subsequently, the release of oxygen radicals induces nuclear translocation of transcriptional regulators, which transform the cardiomyocyte into a more resilient cell. Although preconditioning was initially recognized as protecting only against infarction, PC also limits postischemic dysrhythmias and enhances contractile function. Phase I (safety) and phase II (efficacy) clinical trials now persuasively support pharmacological preconditioning as a safe mode of preventing postcardiac surgical complications. Indeed, preconditioning is currently being proposed as adjunctive to hypothermic perfusates in protecting against the obligate organ ischemia during transplantation.

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Exogenous Calcium Preconditions Myocardium from Patients Taking Oral Sulfonylurea Agents

Cited by 2 publications

References 37 publications

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Ischemic Preconditioning: Fact or Fantasy?

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Exogenous Calcium Preconditions Myocardium from Patients Taking Oral Sulfonylurea Agents

Cited by 2 publications

References 37 publications

Negative inotropic drugs alter indexes of cytosolic [Ca2+]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca2+]-left ventricular pressure relationships after ischemia

Ischemic Preconditioning: Fact or Fantasy?

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Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia