Myocarditis Secondary to Mesalamine-Induced Cardiotoxicity in a Patient with Ulcerative Colitis

Abstract

Development of cardiac manifestations in patients diagnosed with inflammatory bowel disease undergoing treatment with mesalamine is a rare. When this occurs, it can be difficult to tease out the primary etiology, as both IBD and mesalamine can cause cardiac manifestations independently of each other. The exact mechanism of mesalamine-induced cardiotoxicity is yet to be determined although several mechanisms have been described. We present the case of a gentleman with nonexertional chest pain in the setting of ulcerative colitis exacerbation believed to have occurred secondary to mesalamine.

Mesalazine Induces Oxidative Stress and Cytochrome c Release in Isolated Rat Heart Mitochondria: An Analysis of Cardiotoxic Effects

“…Rhodamine123, as a cationic fluorescent dye, was used for the evaluation of MMP collapse. As shown in Figure 3, different concentrations of mesalazine (25,50, and 100 mM) significantly increased rhodamine123 release from rat heart mitochondria over 60 minutes of exposure (5, 30, and 60 min). Also, mesalazine at 100 mM significantly increased rhodamine123 release from mitochondria (P < 0.0001).…”

“…The main mechanism of mesalazine-induced cardiotoxicity is unknown, but there are several possible mechanisms in this regard. 25 One hypothesis is inhibition of COX enzyme by mesalazine and accelerated metabolism of arachidonic acid through lipoxygenases. Inhibition of COX leads to the overproduction of cytokines and initiating a hypersensitivity reaction.…”

“…Mitochondrial swelling as a criterion of mitochondrial membrane permeability was measured by monitoring the decreased absorbance of mitochondrial suspension at 540 nm (A540). As shown in Figure 4, addition of different concentrations of mesalazine (25,50, and 100 mM) to the rat heart mitochondria over 60 minutes of exposure (5, 30, and 60 min) leads to mitochondrial swelling in a concentration-and time-dependent manner. CaCl 2 (100 mM), a known inducer of MPT, was used as a positive control.…”

“…Effect of mesalazine on reactive oxygen species formation in isolated rat heart mitochondria. Freshly isolated mitochondria were incubated with the various concentrations of mesalazine(25, 50, and 100 mm) for 1 hour. Reactive oxygen species was measured by 2 0 ,7 0dichlorofuorescin diacetate staining with spectrofluorescence method.…”

Genetic Basis of Myocarditis: Myth or Reality?

“…Etiologic hypotheses include systemic autoimmune diseases [164][165][166][167][168], drug toxicity [169], infections [170][171][172], and complex combination of autoimmunity, infections and drug toxicity [173]. Infections reported in GCM include coxsackie B2 virus [170], parvovirus B19 [171], HCMV [172] and HIV1 infection [173][174][175][176][177][178][179][180][181][182][183][184]. In most cases, GCM is an isolated entity, while in about one-fifth of cases GCM occurs in association with autoimmune/immune-mediated diseases (Table 4.7), infections, drug toxicity, or syndromes such as immune reconstitution inflammatory syndrome (IRIS) in patients undergoing highly active antiretroviral therapy (HAART) against human immunodeficiency virus type 1 (HIV-1) [173,184,185] or even in patients taking common medications such as amoxicillin [183].…”