Influence of Allopurinol Plus Verapamil Treatment on Myocardial Tissue Necrosis During Permanent Coronary Occlusion in Canine Hearts with Small Infarcts

Kingma, Jr Jg; Denniss, A.R.; Yellon, Derek M.

doi:10.1097/00005344-198907000-00003

Cited by 10 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Myocardial Protectionmentioning

confidence: 99%

“…Animal studies (27)(28)(29)(30) have shown both antinecrosis and antiarrhythmic effects with a host of pharmacological agents that modulate different intraand extracellular mechanisms. Indeed, Kingma et al (27,28), Denniss et al (29) and Werns et al (30) have documented significant reductions of infarct size in animal preparations of chronic coronary artery occlusion in the absence of restoration of blood flow. Acute myocardial infarction significantly lowers vasoregulatory capacity, which probably contributes to reducing contractile dysfunction; however, postischemic deficits in cardiac contractile function (ie, myocardial stunning/hibernation) are dependent on the duration or severity of the ischemic insult and on the adequacy of return of blood flow to reversibly injured myocardium (31,32).…”

Section: Myocardial Protectionmentioning

confidence: 99%

See 1 more Smart Citation

Coronary vasoregulation in health and disease

Kingma

Rouleau

2007

Canadian Journal of Cardiology

View full text Add to dashboard Cite

E arly interests of clinical researchers at the Quebec HeartInstitute focused on various aspects of cardiac physiology, biochemistry (ie, metabolism) and pathology. In the late 1970s, the Quebec Heart Institute recruited Dr Jacques Rouleau, a cardiologist whose primary research interests focused on biophysical mechanisms that regulate the distribution of blood flow across the ventricular wall. The later addition to this laboratory of Dr John Kingma, whose research focused on mechanisms involved in myocardial protection following ischemia-reperfusion injury, created a basic scienceclinical research collaboration that continues today.The principal function of the heart is to supply the different organs in the body with blood containing essential nutrients and oxygen required for their proper functioning. In addition, the heart is essential for the transport of metabolic waste products, the accumulation of which would influence organ function. Mechanical work necessary to pump blood is performed by the myocardium. Proper functioning of the myocardium depends on blood flow in the coronary circulation, which comprises large epicardial conductance vessels originating from the coronary ostia. These large vessels branch into smaller vessels that supply the capillary network responsible for the transport of oxygen and nutrients to the myocytes. Comprehension of mechanisms responsible for regulation of the coronary circulation requires the interpretation of information from several disciplines, including cardiology, physiology, biochemistry and physics; this list is far from exclusive because new information regarding interactions of molecular and mechanical signals is consistently being added to the equation. The present review summarizes several achievements resulting from this research collaboration over the past two decades. REGULATION OF THE DISTRIBUTION OF MYOCARDIAL BLOOD FLOWControl of the coronary circulation involves a host of interactions among mechanical factors, such as arterial pressure, blood flow, ventricular contraction and myocardial wall tension. Suffice it to say that coronary blood flow is never constant but rather adaptive in relation to the metabolic and oxygen requirements of the myocardium; approximately 70% of oxygen transported is extracted from blood flowing in arterial vessels. This intrinsic capacity of arterial vessels to adjust in calibre and maintain constant perfusion over a range of arterial pressures is referred to as 'coronary autoregulation' (Figure 1). Principal mechanisms involved in the control of coronary blood flow include metabolic mediator(s) between myocytes and vascular cells, myogenic tone (induced by stretch) and neurogenic stimulation. However, studies on flow control mechanisms in the coronary circulation are limited because function of intramyocardial resistance vessels cannot be investigated with the currently available techniques. Exercise-induced increases in myocardial oxygen demand are accommodated by increases in coronary blood flow, the latter being controlled by ...

show abstract

Section: Myocardial Protectionmentioning

confidence: 99%

Section: Myocardial Protectionmentioning

confidence: 99%

Coronary vasoregulation in health and disease

Kingma

Rouleau

2007

Canadian Journal of Cardiology

View full text Add to dashboard Cite

show abstract

“…Since conversion of xanthine oxidase by ischaemia is probably mediated by a calcium-activated proteolytic reaction (McCord 1985), xanthine oxidase could be one of the sites of the action of verapamil. This possibility was supported by recent studies by Kingma et al (1987Kingma et al ( , 1989. They observed that pretreatment with allopurinol, verapamil or a combination of the two agents limited myocardial infarct size to a similar extent in the canine heart (Kingma er a/.…”

Section: Discussionmentioning

confidence: 77%

Does Verapamil Limit Myocardial Infarct Size in a Heart Deficient in Xanthine Oxidase?

Adachi

Miura

Noto

et al. 1990

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. The delay of ischaemic myocardial necrosis by verapamil has been reported in the dog heart, which contains a high level of xanthine oxidase, a potential source of cytotoxic free radicals. To test whether the retardation of ischaemic myocyte death by verapamil is not an isolated phenomenon in the xanthine oxidase rich heart, we assessed the effect of verapamil in the rabbit heart, which lacks xanthine oxidase. 2. Verapamil (200 micrograms/kg, i.v. bolus plus 40 micrograms/kg per min) was administered in a group of rabbits (n = 5) to test the haemodynamic response to this agent. The heart rate, blood pressure and left ventricular dp/dt max were reduced by 11, 25 and 57%, respectively, and the plasma concentration of verapamil was maintained at 300-400 ng/mL during the infusion. 3. In other groups of rabbits, the effect of the same dosage of verapamil on the size of myocardial infarct after 20 or 30 min ischaemia and 72 h reperfusion was examined. The verapamil was administered for 45 min, starting 15 min prior to ischaemia. The percentage of area at risk infarcted (%I/AAR) was 15.2 +/- 3.9% in the 20 min ischaemia control group and 15.4 +/- 4.5% in the 20 min ischaemia verapamil group, 49.1 +/- 3.4% in the 30 min ischaemia control group and 41.2 +/- 3.3% in the 30 min ischaemia verapamil group. The %I/AAR was significantly smaller in the 20 min ischaemia control groups and 15.4 +/- 4.5% in the 20 min ischaemia there was no difference in %I/AAR between the control and verapamil treated animals in either the 20 or the 30 min ischaemia groups. 4. These results suggest that verapamil does not delay the transition from reversible to irreversible myocardial injury during coronary occlusion in the rabbit, which like the human, lacks myocardial xanthine oxidase.

show abstract

Kinetic Magnetic‐Field Effect Involving the Small Biologically Relevant Inorganic Radicals NO and O₂^.−

et al. 2011

View full text Add to dashboard Cite

Oxidation of dihydrorhodamine 123 (DHR) to rhodamine 123 (RH) by oxoperoxonitrite (ONOO(-)), formed through recombination of NO and O(2)(·-) radicals resulting from thermal decomposition of 3-morpholinosydnonimine (SIN-1) in buffered aerated aqueous solution at pH 7.6, represents a kinetic model system of the reactivity of NO and O(2)(·-) in biochemical systems. A magnetic-field effect (MFE) on the yield of RH detected in this system is explored in the full range of fields between 0 and 18 T. It is found to increase in a nearly linear fashion up to a value of 5.5±1.6 % at 18 T and 23 °C (3.1±0.7 % at 40 °C). A theoretical framework to analyze the MFE in terms of the magnetic-field-enhanced recombination rate constant k(rec) of NO and O(2)(·-) due to magnetic mixing of T(0) and S spin states of the radical pair by the Δg mechanism is developed, including estimation of magnetic properties (g tensor and spin relaxation times) of NO and O(2)(·-) in aqueous solution, and calculation of the MFE on k(rec) using the theoretical formalism of Gorelik at al. The factor with which the MFE on k(rec) is translated to the MFE on the yield of ONOO(-) and RH is derived for various kinetic scenarios representing possible sink channels for NO and O(2)(·-). With reasonable assumptions for the values of some unknown kinetic parameters, the theoretical predictions account well for the observed MFE.

show abstract

Influence of Allopurinol Plus Verapamil Treatment on Myocardial Tissue Necrosis During Permanent Coronary Occlusion in Canine Hearts with Small Infarcts

Cited by 10 publications

References 0 publications

Coronary vasoregulation in health and disease

Coronary vasoregulation in health and disease

Does Verapamil Limit Myocardial Infarct Size in a Heart Deficient in Xanthine Oxidase?

Kinetic Magnetic‐Field Effect Involving the Small Biologically Relevant Inorganic Radicals NO and O₂^.−

Contact Info

Product

Resources

About

Influence of Allopurinol Plus Verapamil Treatment on Myocardial Tissue Necrosis During Permanent Coronary Occlusion in Canine Hearts with Small Infarcts

Cited by 10 publications

References 0 publications

Coronary vasoregulation in health and disease

Coronary vasoregulation in health and disease

Does Verapamil Limit Myocardial Infarct Size in a Heart Deficient in Xanthine Oxidase?

Kinetic Magnetic‐Field Effect Involving the Small Biologically Relevant Inorganic Radicals NO and O2.−

Contact Info

Product

Resources

About

Kinetic Magnetic‐Field Effect Involving the Small Biologically Relevant Inorganic Radicals NO and O₂^.−