Interrelation between alterations in pulmonary mechanics and hemodynamics in acute myocardial infarction.

Pulmonary mechanics were evaluated in 30 patients with acute myocardial infarction by measuring forced expiratory flow rates and total pulmonary resistance (R(T)) with the oscillometric method at the resonant frequency of the chest (6-8) cycle/s). During the first 3 days after infarction, forced expiratory volume (FEV) and forced mid-expiratory flow rate (FEF(25-75%)) were 69% and 60% of predicted values, respectively. 10 or more wk later these values were 95% and 91%. Initially, R(T) was 52% greater than predicted, but was only 4% greater 10 or more wk later. In 11 patients R(T) was measured at both resonant frequency and at 3 cycle/s. Five of these patients had no clinical signs of heart failure, but nine had abnormally high values of pulmonary artery pressure, "wedge" pressure and pulmonary extravascular water volume. All of these patients recovered. Initially, R(T) at resonance was 50% and R(T) at 3 cycle/s was 130% greater than predicted values. 2-3 wk later these figures were -3% and +6% of those predicted, respectively. At 10 wk or more, significant frequency dependence of R(T) had disappeared (R(T) at 3 cycle/s was 7% greater than R(T) at resonance). Isoproterenol inhalation in six patients caused no change in flow rates, R(T) at resonance, or R(T) at 3 cycle/s. R(T) at resonance and at 3 cycle/s, FEV, and FEF(25-75%) correlated significantly with the pulmonary vascular pressures. Patients with more marked arterial hypoxia and larger values for extravascular water volume had greater elevations of R(T) and depression of FEF(25-75%), but linear correlations were not significant. Clinical signs of congestive heart failure significantly correlated with a fall in FEV and FEF(25-75%), the development of frequency dependence of R(T), and elevation of the pulmonary wedge pressure. The initial elevation of R(T) and low flow rates indicate a modest degree of airway obstruction in acute myocardial infarction. Lack of response to isoproterenol suggests that bronchial muscular constriction is not a major factor. Frequency dependence of R(T) accompanied by elevated pulmonary vascular pressures and extravascular water volume indicates that pulmonary congestion causes the development of uneven time constants in the airways. Vascular engorgement and interstitial edema from elevated vascular pressures causing narrowing of the peripheral airways and closure of collateral airways could account for the above findings.

NKX6.1 functions as a metastatic suppressor through epigenetic regulation of the epithelial-mesenchymal transition.

The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic ß-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6.1 suppresses cell invasion by inhibiting the epithelial-to-mesenchymal transition (EMT). NKX6.1 directly enhances the mRNA level of E-cadherin by recruiting BAF155 coactivator and represses that of vimentin and N-cadherin by recruiting RBBP7 (retinoblastoma binding protein 7) corepressor. Clinical cancer tumors with metastasis show low NKX6.1 protein expression coinciding with low E-cadherin and high vimentin expression. Our results demonstrate that NKX6.1 functions as an EMT suppressor by interacting with different epigenetic modifiers, making it a potential novel therapeutic option.

Early care of acute myocardial infarction.

A fixed life support station (LSS) was established in the emergency department of a community hospital in order to provide early care for patients with suspected acute myocardial infarction (MI). Prospective studies were conducted on 154 patients with verified acute MI. Median time from onset of symptoms to electrocardiographic monitoring was 164 minutes. Overall hospital mortality for these patients was 15.6%. Of 112 patients less than 70 years old, 51 arrived within two hours; only three (6%) of the 51 died. Patients arriving within two hours of the onset of symptoms in clinical class I had an incidence of cardiogenic shock (CS) of 2%, while those arriving two hours or more after the onset of symptoms in clinical class II had an incidence of CS of 26% (P less than .005). A fixed LSS in a community hospital is feasible and effective for early care of patients with acute MI and may facilitate identification of patients at highest risk for development of CS.

Hemodynamic and respiratory effects of dezocine, ciramadol, and morphine.

The hemodynamic and respiratory effects of dezocine and ciramadol, two agonist-antagonist analgesics, were compared with those of morphine in 30 patients undergoing diagnostic cardiac catheterization. Each subject received a single intravenous dose of dezocine (0.125 mg/kg), ciramadol (0.6 mg/kg), or morphine (0.125 mg/kg) in a double-blind fashion. Hemodynamic and respiratory parameters were measured at baseline and 5, 10, and 20 minutes after dosing. Dezocine increased the cardiac index (CI; 2.67 to 2.92 L/min/m2), stroke volume index (SVI; 43.6 to 47.6 ml/beat/m2), left ventricular stroke work index (LVSWI; 57.4 to 64.7 gm-m/m2), and pulmonary vascular resistance (PVR; 105.6 to 154.0 dynes X sec/cm5). Ciramadol increased the CI (2.78 to 3.22 L/min/m2), SVI (40.9 to 48.2 ml/beat/m2), LVSWI (51.1 to 57.9 gm-m/m2), and mean pulmonary arterial pressure (PA; 14.7 to 18.9 mm Hg). Morphine had no effect on CI, SVI, LVSWI, PA, or PVR, but it significantly lowered systolic and diastolic blood pressures. There were no appreciable changes in heart rate, left ventricular end-diastolic pressure, mean arterial pressure, or mean pulmonary capillary wedge pressure after any of the drugs. All three drugs significantly decreased systemic vascular resistance. There were no clinically significant changes in respiratory parameters. We conclude that dezocine, ciramadol, and morphine have no clinically important adverse effects on cardiac performance.

Hemodynamic and respiratory effects of morphine and butorphanol.

The hemodynamic effects of butorphanol, a potent synthetic narcotic-antagonist analgesic, were investigated and compared with those of morphine. A total of 20 patients were studied (8 butorphanol, 12 morphine) at the time of diagnostic cardiac catheterization. Butorphanol decreased pH, PCO2, and systemic artery pressure and increased PCO2, cardiac index, and pulmonary artery pressure. Morphine caused similar changes in pH, PO2, systemic artery pressure, and PCO2 but much smaller changes in cardiac index and no change in pulmonary artery pressure. The clinical implications and possible mechanisms are discussed.

Effect of furosemide on hemodynamics and lung water in acute pulmonary edema secondary to myocardial infarction.

Hemodynamic studies were carried out in 19 patients with left ventricular failure complicating acute myocardial infarction. Fourteen patients were studied before and after the intravenous administration of 0.5 mg/kg of furosemide, and five patients served as a control group. Serial measurements included intracardiac pressures, cardiac output and lung water by a double isotope technique. A significant reduction was noted in right atrial (P less than 0.005), pulmonary arterial (P less than 0.0005) and pulmonary wedge pressures (P less than 0.0005) after administration of furosemide. Only the change in right atrial pressure was significantly different from that in the control group (P less than 0.05). Lung water was not changed in 4 patients studied 2 hours after administration of furosemide but was significantly changed in the remaining 10 patients studied 4 to 24 hours after furosemide (P = 0.0001). This change was also significantly different from values in the control group (P less than 0.05). The patients with no reduction in excess lung water also had a smaller reduction in pulmonary wedge pressure and a lower pretreatment stroke work index than the other patients. The mobilization of excess lung water in patients with acute myocardial infarction complicated by left ventricular failure has several features. Despite a prompt diuresis, the reduction in lung water is delayed for at least several hours after the administration of furosemide and may be related to the degree of left ventricular dysfunction. Venodilation may be a major result of treatment with furosemide.

Unstable angina pectoris.

The pathophysiology of unstable angina has been better elucidated in the past five years and has led to more rational therapy. Coronary arteries in patients with unstable angina have atherosclerotic plaques which are often complex and are the site of platelet activation and fibrin deposition. Nitrates, one of the oldest therapies, are efficacious and act not only by dilating coronary vessels but by reducing preload and afterload. Beta blockers have a salutary effect by decreasing myocardial oxygen demand. Calcium channel blockers attenuate smooth muscle contraction and thereby act to decrease coronary artery spasm. Beta blockers and calcium channel blockers are equally efficacious in unstable angina. The antiplatelet agent, aspirin, has been shown to reduce fatal or non-fatal myocardial infarction and probably overall mortality. The use of heparin acutely for unstable angina has been demonstrated to decrease refractory angina and myocardial infarction, and acutely is probably better than aspirin. For patients with reduced ejection fractions (0.30-0.49), a prospective randomized trial has shown that coronary artery bypass graft surgery offers an improved three-year survival compared with medical therapy; however, surgery does not prevent myocardial infarction. Percutaneous transluminal coronary angioplasty may be a reasonable therapeutic alternative for some patients with single-vessel disease who are refractory to medical therapy but there are as yet no controlled trials of this question. To date a clinical benefit from thrombolytic therapy has not been demonstrated.

Heart disease in Asians and Pacific-Islanders, Hispanics, and Native Americans.

Heart disease is the leading cause of death for Asian-Americans and Pacific-Islanders, Hispanic-Americans, and Native Americans. Generally, heart disease death rates are lower in these population groups than in Caucasians, with the notable exception of Native Americans under the age of 35. Of particular interest are data for southwestern US Native Americans and Mexican-Americans, which indicate low CHD prevalence rates despite high rates of obesity, diabetes mellitus, increasing hypertension, and low socioeconomic status. Much more research is needed to explain these and other observations. Intervention in those risk factors already identified is necessary, particularly in prevention of obesity and diabetes.