sodium-bicarbonate and Ventricular-Dysfunction--Left

Tako-tsubo syndrome (TTS) refers to the apical ballooning of the left ventricle observed when angiographic ventriculography is performed in patients presenting with electrocardiographic changes suggestive of acute coronary syndrome (new transient ST-segment deviation (>0.05 mV) or T-wave inversion (>0.2 mV)), mild elevation of cardiac markers, but normal coronary arteries at the angiogram.. A 54-year-old woman developed the characteristic features of TTS 44 hours following nortriptyline overdose. The admission ECG showed increased QRS duration rapidly reversible after sodium bicarbonate infusion. There was a minimal increase in troponin I level. The ECG performed at the time of chest pain revealed deeply negative T waves in leads I, II, III, aVF, V1 to V6 and remained abnormal at 5 weeks follow-up. In contrast, a complete recovery of left ventricular function was observed within one week.. The pathophysiology of TTS, a variant of myocardial stunning, is still incompletely understood but could be related to sympathetic overstimulation. The possibility of TTS following toxic exposure is discussed.

Topics: Antidepressive Agents, Tricyclic; Drug Overdose; Electrocardiography; Female; Follow-Up Studies; Humans; Middle Aged; Nortriptyline; Sodium Bicarbonate; Takotsubo Cardiomyopathy; Troponin I; Ventricular Dysfunction, Left

To determine the site of thioridazine-induced cardiotoxicity and investigate the effectiveness of sodium bicarbonate (NaHCO3) therapy, isolated rat hearts were perfused with Krebs-Henseleit-Bicarbonate buffer (KHB) at a constant coronary flow of 10 mL/min and electrically paced at 300 bpm. Experimental protocol included 15 min intervals of KHB, thioridazine (TDZ), TDZ + NaHCO3, KHB. Left ventricular (LV) pressure was measured with a balloon-tipped catheter placed in the LV via the mitral valve. Coronary perfusion pressure was monitored continuously as an index of coronary vascular resistance (CVR). LV generated pressure (LVGP) was used as our index of cardiac function and was calculated by subtracting LV end diastolic pressure (LVEDP) from LV peak systolic pressure (LVPSP). TDZ at 7,500 ng/mL was chosen as the toxic dose. NaHCO3 treatment was at an approximate sodium = 155 mM and pH = 7.60. Hearts perfused with TDZ resulted in a progressive decrease in LVGP. After 15 min of TDZ perfusion, LVGP decreased by 50%, and 75% at 30 min (n = 5). TDZ increased LVEDP and decreased LVPSP. TDZ perfusion increased CVR by 83%. In another experiment, hearts were perfused with TDZ for 15 min and then for an additional 15 min with TDZ + NaHCO3. NaHCO3 treatment transiently (approximately 5 min) increased LVGP by 23% (n=5). During NaHCO3 treatment, LVPSP increased and LVEDP and CVR decreased during the first 5 min. During the remainder of the NaHCO3 protocol, the hearts failed, similar to TDZ alone. TDZ diminished left ventricular function and promoted coronary artery vasoconstriction. NaHCO3 temporariy reversed these toxic effects.

Topics: Animals; Cardiotonic Agents; Dopamine Antagonists; Dose-Response Relationship, Drug; Heart; In Vitro Techniques; Male; Rats; Rats, Sprague-Dawley; Sodium Bicarbonate; Thioridazine; Ventricular Dysfunction, Left