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1.
J Cardiovasc Pharmacol ; 23(5): 792-8, 1994 May.
Article in English | MEDLINE | ID: mdl-7521463

ABSTRACT

We wished to provide comparative information regarding the direct effects of flosequinan, a novel quinolone under development for treating heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--milrinone, ouabain, captopril and diltiazem--that have been used to treat heart failure patients, as well as for flosequinoxan, which is the primary metabolite of flosequinan. Flosequinan produced a potent and balanced relaxant effect on norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations, flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with flosequinan and flosequinoxan in the following ways: Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations; ouabain produced both vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of flosequinan and flosequinoxan is unique as compared with that of other agents that have been used to treat patients with heart failure.


Subject(s)
Muscle, Smooth, Vascular/drug effects , Myocardial Contraction/drug effects , Quinolines/pharmacology , Vasodilator Agents/pharmacology , Captopril/pharmacology , Diltiazem/pharmacology , Heart Failure/drug therapy , Humans , In Vitro Techniques , Milrinone , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/metabolism , Ouabain/pharmacology , Pyridones/pharmacology , Pyridones/therapeutic use , Quinolones/pharmacology
2.
Eur J Pharmacol ; 236(3): 363-6, 1993 Jun 04.
Article in English | MEDLINE | ID: mdl-8395383

ABSTRACT

The goal of this study was to assess the relationship between the positive inotropic response to high concentrations of the vasodilators flosequinan and BTS 53 554 (the sulfone metabolite of flosequinan) and the effect of both compounds on different forms of cyclic nucleotide phosphodiesterase. In addition, the relationship between inotropic activity and phosphodiesterase inhibition for the cardiotonic milrinone was also evaluated. All three agents exerted a positive inotropic effect on human cardiac muscle fibers. The concentration of milrinone required to increase cardiac contractility was comparable to the concentration required to inhibit the milrinone-sensitive subclass of cyclic AMP-specific phosphodiesterase (type III phosphodiesterase). However, no such relationship was observed for flosequinan and BTS 53 554. These results suggest that the cardiac response to high concentrations of flosequinan and BTS 53 554 is not mediated by inhibition of type III phosphodiesterase.


Subject(s)
Myocardial Contraction/drug effects , Phosphodiesterase Inhibitors/pharmacology , Pyridones/pharmacology , Quinolines/pharmacology , Quinolones/pharmacology , Humans , In Vitro Techniques , Milrinone , Phosphoric Diester Hydrolases/metabolism , Vasodilation/drug effects
3.
Ann Thorac Surg ; 47(4): 529-32, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2712626

ABSTRACT

The risks of homologous blood transfusion are well documented and recently increased with the emergence of acquired immunodeficiency syndrome. Preoperative autologous donation has been suggested to reduce these risks. This is a report concerning 104 consecutive adult autologous donors (group 1) who had an elective cardiac operation. A similar group of 111 patients operated on during the same period but without autologous blood donation was used for comparison (group 2). Both groups contained similar numbers of patients with coronary artery disease, valvular disease, and mixed lesions, and both had several patients with atrial septal defects. Group 2 patients (mean age, 67.8 years) were significantly older than group 1 patients (mean age, 58.9 years) (p less than 0.05). The mean donation in group 1 was 4.1 units, but 12 (11.5%) had to discontinue donations. Increasing angina in 10 (12.2%) of the 82 patients with coronary artery disease was the most common complication, and necessitated hospitalization in two instances. In 77 (75.5%) of the 102 group 1 patients who had operation and 23 (21%) of the 110 group 2 patients, no homologous blood products were required. Group 1 patients used significantly less homologous fresh frozen plasma (0.1 unit versus 0.97 unit; p less than 0.005) and packed red blood cells (0.6 unit versus 2.1 units; p less than 0.001) than group 2 patients. Group 1 patients received 3.3 and 3.1 units of autologous packed cells and plasma, respectively. No complications of autologous transfusion were seen. Predonation of autologous blood is an effective, safe method of reducing homologous blood requirements in elective cardiac operations, but it does carry some risk, especially in patients with coronary artery disease.


Subject(s)
Blood Transfusion, Autologous , Cardiac Surgical Procedures/methods , Adult , Hematocrit , Humans , Middle Aged , Reoperation
4.
Ann Thorac Surg ; 43(5): 568-9, 1987 May.
Article in English | MEDLINE | ID: mdl-3555373

ABSTRACT

A simple technique for replacing a valve prosthesis within a composite aortic root graft is described. This method allows isolated valve replacement without removing the Dacron tube graft or altering the original coronary artery repair.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Aortic Valve/surgery , Humans , Methods , Reoperation , Suture Techniques
5.
Ann Thorac Surg ; 38(6): 606-10, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6508416

ABSTRACT

Severe gastroesophageal reflux was found in 9 out of 18 infants with congenital esophageal atresia studied radiographically shortly after primary reconstruction. Pulmonary complications were recorded in 18 out of 32 similar patients in long-term follow-up. Strictures at the level of the anastomosis were detectable in 18 out of 32 patients; eleven strictures were severe enough to require dilation or surgical revision. These findings suggest that early evaluation for gastroesophageal reflux may be useful in management of infants with esophageal atresia. The precautions taken preoperatively to prevent complications of gastroesophageal reflux should be continued in the postoperative interval unless a competent lower esophageal sphincter is demonstrated.


Subject(s)
Esophageal Atresia/surgery , Esophageal Atresia/complications , Esophageal Atresia/diagnostic imaging , Esophageal Stenosis/diagnostic imaging , Esophageal Stenosis/etiology , Follow-Up Studies , Humans , Infant , Lung Diseases/etiology , Radiography
6.
Epilepsia ; 17(4): 395-402, 1976 Dec.
Article in English | MEDLINE | ID: mdl-137114

ABSTRACT

Blockade of tonic hindlimb extension (THE) in the maximal electroshock seizure test was demonstrated for C-28'882-Ba, a muscle spindle suppressant, chlorpromazine, a depressant of fusimotor drive, and gallamine, a neuromuscular blocking drug. These agents also blocked THE produced by very large doses of pentylenetetrazol. Dantrolene, a muscle contraction antagonist, and MI-65-S, a muscle spindle suppressant, significantly delayed THE. The data indicate that blockade of THE may be effected at a multiplicity of loci and may not be an expression of an "anticonvulsant" effect.


Subject(s)
Anticonvulsants/pharmacology , Muscle Contraction/drug effects , Muscle Spindles/drug effects , Muscles/drug effects , Animals , Chlorpromazine/pharmacology , Dantrolene/pharmacology , Electroshock , Gallamine Triethiodide/pharmacology , Hindlimb , Male , Mice , Pentylenetetrazole , Seizures/chemically induced
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