Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

Abstract

Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were infused with isoproterenol (ISO; 2.5 mg/kg/day subcutaneous [sc]), a beta-adrenergic agonist, for 28 days and subsequently exposed to PM by inhalation. ISO induced tachycardia and hypotension throughout treatment followed by postinfusion decrements in heart rate, contractility, and blood pressures (systolic, diastolic, pulse), and fibrotic cardiomyopathy. Changes in heart rate and heart rate variability (HRV) 17 days after ISO cessation indicated parasympathetic dominance with concomitantly altered ventilation. Rats were subsequently exposed to filtered air or Harvard Particle 12 (HP12) (12 mg/m(3))--a metal-rich oil combustion-derived PM--at 18 and 19 days (4 h/day) after ISO infusion via nose-only inhalation to determine if cardio-impaired rats were more responsive to the effects of PM exposure. Inhalation of PM among ISO-pretreated rats significantly increased pulmonary lactate dehydrogenase, serum high-density lipoprotein (HDL) cholesterol, and heart-to-body mass ratio. PM exposure increased the number of ISO-pretreated rats that experienced bradyarrhythmic events, which occurred concomitantly with acute alterations of HRV. PM, however, did not significantly affect mean HRV in the ISO- or saline-pretreated groups. In summary, subchronic ISO treatment elicited some pathophysiologic and histopathological features of heart failure, including cardiomyopathy. The enhanced sensitivity to PM exposure in SHHF rats with ISO-accelerated cardiomyopathy suggests that this model may be useful for elucidating the mechanisms by which PM exposure exacerbates heart disease.

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

“…A host of cardiac alterations consistent with the pathogenesis of heart failure have been revealed following continuous ISO infusion with subcutaneously implanted osmotic pumps [76,90,132,139,142,144,146,157,[160][161][162][163][164][165][166][167]. Infusion of 2.4 mg/kg/day ISO in Wistar rats caused less than 5% mortality while it altered gene expression in a strikingly similar magnitude and time-course as aortic constriction through day 8 of infusion; however, most of these changes reverted after 26 days of infusion [132].…”

“…ISO has been shown in several studies to cause tachycardia, hypotension, Ca 2? overload, free radical generation, coronary vasospasm, high-energy phosphate exhaustion, and impaired myocardial glucose metabolization in the short term, as well as decreased SERCA expression, ryanodine receptor PKA hyperphosphorylation, and bAR down-regulation and uncoupling in the long term that lead to a progression from myocardial hypoxia to ischemia, inflammation, necrosis, apoptosis, and fibrosis accompanied by HF-like symptoms [90,134,[142][143][144][145][146][147][148][149]. Ultimately, these alterations in the myocardium decrease contractility and heart rate while increasing water and Na ?…”

“…Thus, heart failure in the SHHF is not entirely a result of hypertension-induced increases in afterload and may result partly from preload-driven volume overload. Unanesthetized, unrestrained lean male SHHF rats have hypertension exceeding the SHR (24-h MAP: 161 mmHg at 10 weeks and 145 mmHg at 15 weeks) [90,91], while several studies suggest that unanesthetized, unrestrained obese male SHHFs have less severe hypertension (MAP: 119 mmHg at 18-26 weeks, 133 mmHg at 40 weeks, and 127 mmHg at 54 weeks) [92,93]. Some studies have reported higher systolic pressure in the obese relative to the lean; however, pressure measurements in these studies use anesthesia or restraint (e.g., tail-cuff), which may differentially affect the two phenotypes [81,83,85].…”

Optical Analytical Technique for Carbonaceous Particles Using Laser-Induced Electro-Avalanche Fluorescence and Laser-Induced Incandescence

“…As a result, cleaner burning engines often produce smaller specks of soot -nanosize particles -as a by-product. It is also well known that the inhalation of fine particulate matter causes a range of health problems: (1)(2)(3)(4) particles that are smaller than 2.5 μm in size (PM 2.5 ) can penetrate into the gas-exchange region of the lungs. Using existing technologies, it is difficult to analyze (in real time) the size and composition of fine particles over a broad range of conformational space in the atmosphere.…”

Development of sensing system for carbonaceous particles using LIBS combined with LII temporal analytical technique

“…Hence, cleaner-burning engine often produce smaller soot; nanosized particles as a byproduct. It is well known that inhalation of fine particle matter causes several health problems [1][2][3][4]. Particles that are smaller than 2.5 μm in size (PM 2.5 ) can penetrate the gas-exchange region of the lung.…”