A deleterious mutation in the LOXHD1 gene causes autosomal recessive hearing loss in Ashkenazi Jews.

Autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL) in Ashkenazi Jews, is mainly caused by mutations in the GJB2 and GJB6 genes. Here we describe a novel homozygous mutation of the LOXHD1 gene resulting in a premature stop codon (R1572X) in nine patients of Ashkenazi Jewish origin who had severe-profound congenital non-progressive ARNSHL and benefited from cochlear implants. Upon screening for the mutation among 719 anonymous Ashkenazi-Jews we detected four carriers, indicating a carrier rate of 1:180 Ashkenazi Jews. This is the second reported mutation in the LOXHD1 gene, and its homozygous presence in two of 39 Ashkenazi Jewish families with congenital ARNSHL suggest that it could account for some 5% of the familial cases in this community.

Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.

OBJECTIVE: The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. METHODS: This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. RESULTS: Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. CONCLUSIONS: This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

[Non-penetrating deep sclerectomy without collagen implant for glaucoma, as single or combined surgery].

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery. 24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intraocular lens implantation. Mean intraocular pressure decreased from 24.8 +/- 3.9 mmHg initially to 12.8 +/- 4.4 mmHg 6 months after operation (p < 0.0001). There was no difference in postoperative intraocular pressure between DS as a single procedure or as part of a combined operation. Complications were mild and of short duration. If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

Comparison of slow oscillating versus fast balloon inflation strategies for coronary angioplasty.

Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.

Bioresorbable microporous stents deliver recombinant adenovirus gene transfer vectors to the arterial wall.

The use of intravascular stents as an adjunct for percutaneous transluminal revascularization is limited by two principal factors, acute thrombosis and neointimal proliferation, resulting in restenosis. To overcome these limitations, we have investigated the potential of microporous bioresorbable polymer stents formed from poly(L-lactic acid) (PLLA)/poly(epsilon-caprolactone) (PCL) blends to function both to provide mechanical support and as reservoirs for local delivery of therapeutic molecules and particles to the vessel wall. Tubular PLLA/PCL stents were fabricated by the flotation-precipitation method, and helical stents were produced by a casting/winding technique. Hybrid structures in which a tubular sheath is deposited on a helical skeleton were also generated. Using a two-stage solvent swelling technique, polyethylene oxide has been incorporated into these stents to improve hydrophilicity and water uptake, and to facilitate the ability of these devices to function as drug carriers. Stents modified in this manner retain axial and radial mechanical strength sufficient to stabilize the vessel wall against elastic recoil caused by vasoconstrictive and mechanical forces. Because of the potential of direct gene transfer into the vessel wall to ameliorate thrombosis and neointimal proliferation, we have investigated the capacity of these polymer stents to function in the delivery of recombinant adenovirus vectors to the vessel wall. In vitro, virus stock was observed to readily absorb into, and elute from these devices in an infectious form, with suitable kinetics. Successful gene transfer and expression has been demonstrated following implantation of polymer stents impregnated with a recombinant adenovirus carrying a nuclear-localizing betaGal reporter gene into rabbit carotid arteries. These studies suggest that surface-modified polymer stents may ultimately be useful adjunctive devices for both mechanical support and gene transfer during percutaneous transluminal revascularization.

Relation of contractile reserve during low-dose dobutamine echocardiography and angiographic extent and severity of coronary artery disease in the presence of left ventricular dysfunction.

Contractile reserve, during low-dose dobutamine echocardiography, is frequently used for the assessment of myocardial viability in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Whether contractile reserve is affected by the severity of the underlying CAD is presently unknown. Accordingly, we studied 58 patients with stable CAD and LV dysfunction who underwent coronary angiography and low-dose dobutamine echocardiography. In each vascular region the worst stenosis was identified and quantitated as percent diameter stenosis. Segmental wall motion during echocardiography was scored visually and rest and dobutamine wall motion score indexes were calculated. Contractile reserve was defined as > or = 1 grade improvement in wall motion score of > or = 2 contiguous segments along with > or = 20% reduction in global wall motion score index with dobutamine. There was no difference between patients with (n = 26) and without (n = 32) contractile reserve in percent coronary stenosis (89 +/- 17% vs 87 +/- 17%, p = 0.6), number of coronary arteries with > 50% diameter stenosis (2.0 +/- 0.8 vs 2.2 +/- 0.7, p = 0.4), number of occluded coronary arteries (1.2 +/- 0.9 vs 1.1 +/- 0.9, p = 0.6), or the prevalence of collaterals demonstrated angiographically (61% vs 56%, p = 0.5). Our data demonstrates that in patients with CAD and LV dysfunction, the prevalence of contractile reserve during low-dose dobutamine echocardiography is independent of the angiographic extent and severity of CAD.

A critical reappraisal of the oximetric assessment of intracardiac left-to-right shunting in adults.

Although the oximetric analysis of blood from the right heart chambers is the most commonly used method for assessing the presence of intracardiac left-to-right shunting, the data the analysis is based on are limited. In addition, uncertainty exists concerning the best way of estimating the mixed venous oxygen content in subjects with intraatrial left-to-right shunting. In 102 adults without left-to-right shunting, blood was obtained from the venae cavae and right heart chambers to measure oxygen content. The limits of normality of oxygen content differences were 0.5 ml/dl from venae cavae to right atrium, 0.6 ml/dl from right atrium to right ventricle, and 0.9 ml/dl from right ventricle to pulmonary artery. The pulmonary arterial oxygen content was best estimated by combining the superior and inferior vena caval oxygen contents according to the formula (2[SVC] + 3[IVC]) divided by 5, where SVC is the superior vena cava and IVC is the inferior venae cava. These data provide new oximetric criteria for establishing the presence of intracardiac left-to-right shunting in adults.

Effects of intranasal cocaine on sympathetic nerve discharge in humans.

Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these excitatory and inhibitory neural influences determines the net effect of cocaine on sympathetic discharge targeted to the human skeletal muscle circulation.

Comparison of quantitation of left ventricular volume, ejection fraction, and cardiac output in patients with atrial fibrillation by cine magnetic resonance imaging versus invasive measurements.

Currently available invasive and noninvasive techniques for the determination of left ventricular end-diastolic and end-systolic volumes, ejection fraction, and cardiac output are more time-consuming and potentially less accurate in patients with atrial fibrillation (AF) than in those with sinus rhythm. Although magnetic resonance imaging (MRI) can rapidly and accurately measure these variables in patients with sinus rhythm, its ability to do so in subjects with AF is not known. To determine if left ventricular volumes, ejection fraction, and cardiac output can be measured accurately in patients with AF using MRI, 26 subjects (13 women and 13 men, aged 15 to 76 years) in sinus rhythm (n = 13) or AF (n = 13) underwent MRI followed immediately by invasive measurements of these indexes. For those in AF, MRI measurements of left ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and cardiac output correlated well with catheterization measurements (r = 0.90, 0.90, 0.95, 0.85, and 0.90, respectively). In addition, the mean difference between MRI and catheterization measurements was similar in subjects with AF and in those with sinus rhythm. Compared with standard invasive measurements, MRI provides an accurate noninvasive determination of left ventricular volumes, ejection fraction, and cardiac output in patients with AF.

Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions.

PURPOSE: Nicotine replacement therapy has become a popular therapy for smokers attempting to stop smoking. Unfortunately, some subjects continue to smoke while receiving it. Since nicotine is believed to be the primary constituent of cigarette smoke responsible for its acute adverse effects on myocardial oxygen supply and demand, concomitant nicotine replacement therapy and smoking theoretically could provoke a marked decrease in myocardial oxygen supply and increase in demand. This study was performed to assess the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) myocardial oxygen demand, (b) coronary arterial dimensions, and (c) the development of acute cardiovascular tolerance. PATIENTS AND METHODS: In 19 smokers referred for cardiac catheterization for the evaluation of chest pain, we assessed the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) heart rate-systolic arterial pressure product (an estimate of myocardial oxygen demand), (b) coronary arterial dimensions (measured with computer-assisted quantitative arteriography), and (c) the development of acute cardiovascular tolerance. RESULTS: Smoking a first cigarette increased rate pressure product (P < 0.001) and decreased coronary arterial dimensions (P < 0.0001). Subsequently, neither variable was altered by intranasal nicotine spray or a second cigarette. Despite a substantial increase in serum nicotine concentration with nicotine spray and smoking, acute cardiovascular tolerance appears to develop. CONCLUSIONS: Cigarette smoking causes an increase in myocardial oxygen demand and concomitant coronary arterial vasoconstriction. However, further increases in the serum nicotine concentration do not cause a greater increase in demand or decrease in coronary arterial dimensions. These data suggest that humans acutely develop tolerance to an increasing nicotine concentration, thereby helping to explain the apparent lack of a potential synergistic adverse effect associated with continued smoking during nicotine replacement therapy.

Improved bioresorbable microporous intravascular stents for gene therapy.

Drug imbibing microporous stents are under development at a number of centers to enhance healing of the arterial wall after balloon coronary angioplasty procedures. The authors improved the mechanical strength and reservoir properties of a biodegradable microporous stent reported to this Society in 1994. A combined tubular/helical coil stent is readily fabricated by flotation/precipitation and casting/ winding techniques. A two stage solvent swelling technique allows precise adjustment of the surface hydrophilic/hydrophobic balance. These developments permit seven-fold improvement in drug capacity without significantly altering mechanical properties. Stents modified in this manner retain tensile and compressive strength and are suitable for remote deployment. Elution kinetics of these modified stents suggest they are suitable for gene delivery. Successful gene transfer and transmural expression have been demonstrated after implantation of stents impregnated with a recombinant adenovirus carrying a nuclear localizing beta-galactosidase reporter gene into rabbit carotid arteries. These studies suggest that surface modified, bioresorbable polymer stents ultimately may be useful adjunctive devices for gene transfer during percutaneous transluminal revascularization.

Incidence and treatment of elastic recoil occurring in the 15 minutes following successful percutaneous transluminal coronary angioplasty.

This study was performed (1) to assess the incidence and magnitude of elastic recoil occurring within 15 minutes of successful coronary angioplasty, and (2) to determine the effect of subsequent additional balloon inflations on coronary luminal diameter in patients displaying substantial recoil. The coronary angiograms of 50 consecutive patients who underwent a successful percutaneous transluminal coronary angioplasty were analyzed using computer-assisted quantitative analysis. The patients were divided into 2 groups based on the magnitude of early elastic recoil following angioplasty: those with < or = 10% (group I, n = 30) and those with > 10% (group II, n = 20) loss of minimal luminal diameter as assessed by comparing the angiogram obtained immediately after successful angioplasty with that obtained 15 minutes later. The 2 groups were similar in clinical, angiographic, and procedural characteristics. Of the 20 group II subjects, 18 (90%) underwent repeat balloon dilatations, and 2 patients (10%) had no further intervention. After additional balloon inflations were performed in these 18 patients, 16 (90%) had a final result with < 10% loss of minimal luminal diameter 15 minutes later. In conclusion, elastic recoil 15 minutes after apparently successful percutaneous transluminal coronary angioplasty is frequent, occurring in approximately 40% of patients, and is attenuated in 90% of subjects with additional balloon inflations. The resultant larger lumen diameter may exert a salutary effect on long-term outcome.

Effects of the intracoronary infusion of cocaine on coronary arterial dimensions and blood flow in humans.

This study was done to assess the influence of large concentrations of cocaine (infused into the left coronary artery) on coronary arterial dimensions and blood flow in humans. In 20 subjects undergoing cardiac catheterization, incrementally increasing doses of (1) saline solution (n = 10, controls) or (2) cocaine hydrochloride (n = 10) were infused into the left coronary artery, and the effects on heart rate, systemic arterial pressure, coronary sinus blood flow, and coronary arterial dimensions were measured. Saline solution induced no change in any variable. With the infusion of cocaine, there was an incremental increase in its concentration in the systemic (femoral arterial) and coronary (coronary sinus) circulations (maximal concentrations, 0.14 +/- 0.06 [mean+/-SD] and 3.50 +/- 0.70 mg/L, respectively). At the maximal cocaine infusion rate, heart rate and diastolic arterial pressure increased slightly, but coronary sinus blood flow and the dimensions of nondiseased and diseased coronary arterial segments did not change. Thus, intracoronary infusion of cocaine in an amount sufficient to achieve a high concentration in the coronary circulation does not induce epicardial coronary arterial vasoconstriction or alter blood flow.

Utility of the 12-lead electrocardiogram in identifying underlying coronary artery disease in patients with depressed left ventricular systolic function.

We assessed the utility of the 12-lead electrocardiogram (ECG) in identifying severe coronary artery disease (CAD) in patients with depressed left ventricular (LV) systolic function. In 336 patients referred for cardiac catheterization with LV ejection fractions < 0.50, we compared the 12-lead ECG of those with and without CAD by multivariate analysis. The sensitivities, specificities, and positive and negative predictive values of all dichotomous electrocardiographic variables for identifying the presence of severe CAD were determined. In comparison to subjects with CAD, those without disease were more likely to exhibit left-axis deviation (p = 0.01), left bundle branch block (p < 0.001), or LV hypertrophy (p < 0.001), and less likely to exhibit pathologic inferior Q waves (p < 0.001). The presence of anterior or any Q waves was similar between the groups. The presence of any diagnostic Q wave had a positive predictive value of 92%, sensitivity of 57%, and specificity of 80% for identifying severe CAD. In patients with LV systolic dysfunction, the 12-lead ECG is insensitive and nonspecific for identifying those with concomitant severe CAD.

Assessment of coronary arterial flow and flow reserve in humans with magnetic resonance imaging.

BACKGROUND: The noninvasive measurement of absolute epicardial coronary arterial flow and flow reserve would be useful in the evaluation of patients with coronary circulatory disorders. Phase-contrast magnetic resonance imaging (PC-MRI) has been used to measure coronary arterial flow in animals, but its accuracy in humans is unknown. METHODS AND RESULTS: Twelve subjects (7 men, 5 women: age 44 to 67 years) underwent PC-MRI measurements of flow in the left anterior descending coronary artery or one of its diagonal branches at rest and after administration of adenosine (140 microgram . kg(-1) . min (-1) IV). Immediately thereafter, intracoronary Doppler velocity (IDV) and flow measurements were made during cardiac catheterization at rest and after intravenous administration of adenosine. For the 12 patients, the correlation between MRI and invasive measurements of coronary arterial flow and coronary arterial flow reserve was excellent: coronary flow (MRI) (mL/min)= 0.85 x coronary flow (IDV) (mL/min)+17 (mL/min), r=.89, and coronary flow reserve (MRI) =0.79 x coronary velocity reserve (IDV) + 0.34, r=.89. For the range of coronary arterial flows (18 to 161 mL/min) measured by MRI, the limit of agreement between MRI and catheterization measurements of flow was -13+/-30 mL/min; for the range of coronary reserves (0.7 to 3.7) measured by MRI, the limit of agreement between the two techniques was 0.1+/-0.4. CONCLUSIONS: Cine velocity-encoded PC-MRI can noninvasively measure absolute coronary arterial flow in the left anterior descending artery in humans. PC-MRI can detect pharmacologically induced changes in coronary arterial flow and can reliably distinguish between those subjects with normal and abnormal coronary artery flow reserve.

Influence of metoprolol on heart rate variability in survivors of remote myocardial infarction.

We assessed the influence of metoprolol on heart rate variability in survivors of remote myocardial infarction. In 43 survivors of myocardial infarction 12 to 18 months previously (26 men and 17 women, aged 38 to 69 years), two 24-hour ambulatory electrocardiograms were recorded 2 weeks apart. In patients in group A (n=28), who had taken metoprolol for the previous year, the drug was discontinued for 2 weeks, after which the first recording was done. The second recording was done 2 weeks after metoprolol was resumed. In patients in group B (n=15), who had not taken metoprolol for the previous year, it continued to be withheld, and two 24-hour recordings were done 2 weeks apart. In group A, metoprolol increased the time domain variables indicative of enhanced vagal tone; root-mean-square successive difference in normal RR (NN) intervals was 20 +/- 11 ms (mean +/- SD) without and 24 +/- 9 ms with metoprolol (p<0.05), and the proportion of NN that differ by >50 ms (pNN50%) was 3.6 +/- 6.0 without and 5.5 +/- 6.0 with metoprolol (p<0.05). In the frequency domain, the logarithms of the 24-hour very low frequency and the 24-hour high-frequency power (reflecting parasympathetic activity) were increased (5.12 +/- 1.03 and 4.48 +/- 1.51, respectively, without metoprolol; 5.32 +/- 0.99 and 4.83 +/- 1.24, respectively, with metoprolol, p <0.05 for both). Thus, in survivors of remote myocardial infarction, metoprolol enhances parasympathetic cardiac activity in the time and frequency domain measures of heart rate variability.