The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats.

BACKGROUND: Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats. METHODS: The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues. RESULTS: Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group. CONCLUSION: Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.

Effects of digoxin on cardiac iron content in rat model of iron overload.

BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. METHODS: We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively. RESULTS: Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. CONCLUSION: It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca2+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions.

The prevalence of low physical activity in an urban population and its relationship with other cardiovascular risk factors: Findings of a community-based study (KERCADRS) in southeast of Iran.

BACKGROUND: The low physical activity (LPA) more or less affects every community. Because of high prevalence of cardiovascular diseases in Iran and their relationship with LPA, this study aimed to measure precisely the epidemic size of LPA and determine its relationship with six other coronary artery disease (CAD) risk factors among an urban population aged 15 to 75 years in Kerman, Iran. METHODS: Using household survey, 5895 adults were randomly recruited through single-stage cluster sampling from 250 postal codes. Demographic characteristics, blood pressure, blood glucose, cholesterol, triglyceride, smoking, opium use, mental status and physical activities at work, rest and recreation were assessed and ranked as low, moderate and intense. Adjusted odds ratio (AOR) was reported as a measure of the relationship between LPA and other CAD risk factors. RESULTS: The prevalence of low, moderate, and intense physical activity were 42.1% (40.3-43.9), 45.0% (43.6-47.4) and 12.4% (11.1-13.9), respectively. LPA showed a sudden rise from 36.8% to 45.4% after the age of 25 years. On average, women had less physical activity than men (45.1% vs. 39.2%, P= 0.01). Participants with low physical activity compared to those without physical activity had significantly higher chance of anxiety [odds ratio 1.39; confidence interval (95% CI) 1.08-1.79; P = 0.01], hypertension (1.59; 1.08-2.35; P = 0.02), hyper-cholesterolemia (1.37; 1.06-1.76; P = 0.02), cigarette smoking (1.52; 1.07-2.11; P = 0.01), opium addiction (1.47; 1.07-2.02; P = 0.02) and overweight/obesity (1.34; 1.05-1.71; P = 0.02). CONCLUSION: LPA was very common in the studied population and almost half of the adults were at risk for CAD because of insufficient level of physical activity. Such risky life-style pattern makes the emerging of CAD epidemic unavoidable, if effective interventions not being in place timely to this community.

Hypertension: diagnosis, control status and its predictors in general population aged between 15 and 75 years: a community-based study in southeastern Iran.

OBJECTIVES: Hypertension (HTN) is an important cause of cardiovascular related morbidity and mortality. This study aimed at providing the prevalence of pre-HTN, diagnosed and undiagnosed HTN, along with its control and associated factors in an adult population. METHODS: 5,900 participants aged 15-75 years took part in the study. HTN was verified by examination, self-reported history or using anti-hypertensive drug(s). Pre-hypertension and hypertension were defined as 120-139/80-89 mmHg and >140/>90 mmHg for systolic/diastolic BP, respectively. RESULTS: The prevalence of hypertension was 18.4 % from which 10.5 %were diagnosed and 7.9 % were undiagnosed. The prevalence of pre-HTN was 35.5 %. HTN increased by age (2.4 % in 15-24 to 49 % in 55-64 years). The men had higher pre-HTN (42.7 vs. 28.1 %) and undiagnosed HTN (11.3 vs. 4.6 %). Of those diagnosed, 56.3 % had uncontrolled BP levels. Smoking, anxiety, obesity, and positive family history of HTN were the most significant predictors for HTN. CONCLUSIONS: Hypertension affected almost one-fifth of the population. Given the poor control in diagnosed hypertensive patients, it is alarming that the current health system in urban areas in Iran is not effective enough to control the epidemic spread of non-communicable diseases.

The effect of passive opium smoking on cardiovascular indices of rabbits with normal and ischemic hearts.

Some Asian people believe that opium can protect the cardiovascular system. To assess this belief, we investigated the effect of passive opium smoking (POS) on cardiovascular indices in rabbits with ischemic and non-ischemic hearts.Rabbits (n = 43) were divided into control (CTL), short term opium (SO) and long term opium (LO) groups. SO and LO groups were exposed to opium smoking for 3 days and 4 weeks, respectively. ECG, blood pressure (BP), left ventricular pressure and cardiac troponin I levels were recorded. Isoproterenol (ISO) was injected to induce cardiac ischemia and after 4 h the above variables were measured along with cardiac histopathology assessment.All groups showed significant increments in troponin I level (P < 0.05) except the CTL group. This trend was more obvious in ISO-treated groups. Mean arterial pressure (MAP) significantly decreased in all groups (p< 0.05) except the LO group. Opium exposure attenuated ISO-induced myodegeneration but augmented tissue congestion and hemorrhage.In conclusion, higher troponin I serum level and ECG changes were found in passive opium smoking groups. This evidence is against the belief that opium can protect the cardiovascular system.

Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts.

BACKGROUND: To scientifically test a traditionally belief of some Asian countries residents that opium may prevent or have ameliorating effects on cardiovascular diseases (CVD) we investigated the effect of passive opium smoking (POS) on plasma lipids and some cardiovascular parameters in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. METHODS: 40 rabbits were fed for 2 weeks with cholesterol-enriched diet and divided to control (CTL), short-term opium (SO) and long-term opium (LO) groups. SO and LO groups were exposed to POS for 3 days and 4 weeks respectively. ECG, blood pressure (BP) and left ventricular pressure recorded and serum lipid and cardiac troponin I levels were measured. Isoproterenol (ISO) injected for induction of cardiac ischemia and after 4h the above variables were measured along with cardiac histopathology assessment. RESULTS: HDL cholesterol decreased significantly in LO compared to CTL group (35+/-5 vs 53+/-5mg/dl). Groups treated with ISO showed significantly higher increments in troponin I level (P<0.05) except for LO group and reduction of BP was higher in ISO and SO+ISO groups compared to CTL and SO groups respectively (-38+/-6 vs -23+/-4 and -37+/-11 vs -11+/-3 percent respectively, P<0.05). Reduction in BP was significantly lower in LO+ISO compared to ISO group. Opium exposure caused a trend of increase in blood pressure, LDL cholesterol and ECG disturbances, attenuated ISO induced myonecrosis but augmented tissue congestion and hemorrhage. CONCLUSION: POS can be considered as a CVD risk factor. Opium does not reduce BP or cholesterol level, as is anticipated by its users.