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Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents
L Gregorini1, J Marco, C Palombo
1Clinica Medica Generale, Ospedale Maggiore-IRCCS, University of Milano, Italy. gregorm@imiucca.csi.unimi.it
Insights
Alpha-adrenergic blockers effectively treated left ventricular (LV) dysfunction after transient ischemia in patients. Combining alpha- and beta-blockers negated these beneficial effects, suggesting neural mechanisms in postischemic LV dysfunction.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Postischemic left ventricular (LV) dysfunction mechanisms remain unclear.
- Percutaneous transluminal coronary angioplasty (PTCA) serves as a human model for ischemia-reperfusion.
- LV dysfunction following ischemia is a significant clinical concern.
Purpose of the Study:
- To assess the efficacy of alpha-adrenergic blocking agents in mitigating LV dysfunction post-transient ischemia.
- To investigate the role of neural mechanisms in postischemic LV dysfunction.
Main Methods:
- Fifty patients undergoing coronary stenting for stenosis were studied.
- Transesophageal echocardiography monitored LV function during and after PTCA.
- Patients received intracoronary phentolamine, intravenous urapidil, a combination of phentolamine and propranolol, or saline.
Main Results:
- Significant LV contractile dysfunction occurred post-PTCA in both ischemic and non-ischemic myocardium.
- Alpha-blockers (phentolamine, urapidil) counteracted LV dysfunction, increased coronary resistance, and reduced vasoconstriction.
- Combined alpha- and beta-blockade with phentolamine and propranolol did not improve LV dysfunction.
Conclusions:
- LV dysfunction post-PTCA mirrors findings in animal ischemia models.
- Alpha-blockers effectively resolved LV, macrocirculatory, and microcirculatory dysfunction.
- The opposing effects of alpha- and beta-blockade support a hypothesis of neural mechanisms driving postischemic LV dysfunction.
Objectives:
We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans.
Background:
The mechanisms underlying postischemic LV dysfunction are largely unknown.
Methods:
Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline.
Results:
Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects.
Conclusions:
LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.