Author + information
- Received October 11, 1988
- Revision received December 7, 1988
- Accepted February 6, 1989
- Published online September 1, 1989.
- Stephen A. Morris, MD, PHD∗∗,
- Louis M. Weiss, MD, MPH†,
- Stephen Factor, MD†,
- John P. Bilezikian, MD∗,
- Herbert Tanowitz, MD† and
- Murray Wittner, MD, PHD†
- ↵∗Address for reprints: Stephen A. Morris, MD, Department of Medicine 9–410, College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032.
The influence of long-term verapamil administration on the consequences of Trypanosoma crud infection in mice was studied with regard to animal mortality, morbidity, myocardial pathologic features and myocardial beta-adrenergic adenylate cyclase activity. Verapamil administration dramatically decreased the mortality rate from 60% to 6% during the 70 day period of infection. Three clinical stages of infection were evident. In the acute stage (17 days after infection with maximal parasitemia), verapamil treatment not only decreased the incidence of myocardial disease (fibrosis and inflammation), but also protected myocardial beta-adrenergic adenylate cyclase activity. In addition, there was no increase in total body weight, which was regarded as an index of right-sided heart failure. In the subacute stage (30 to 60 days after infection), administration of verapamil continued to decrease myocardial disease and preserve beta-adrenergic adenylate cyclase activity. In addition, verapamil ameliorated the morbidity and mortality associated with this stage of infection.
The chronic stage of infection was characterized by a decrease in myocardial disease and in beta-adrenergic adenylate cyclase activity. Thus, independent of the state of infection, long-term verapamil treatment enhanced betaadrenergic adenylate cyclase activity. In addition, verapamil ameliorated the morbidity associated with infection. Although the relation among these various effects of verapamil in the setting of T. cruziinfection remains to be determined, collectively the results suggested that verapamil administration attenuated the consequences of T. cruziinfection.
☆ This work was funded in part by Grants HL20859, HL28958, AI12770, HL35882, AI07183 and A126368 from the National Institutes of Health, Bethesda, Maryland.
- Received October 11, 1988.
- Revision received December 7, 1988.
- Accepted February 6, 1989.