SELECTED SUMMARIES

for new powerful anti-secretory drugs, particularly fortreating patients with severe disease.

In studies comparing omeprazole against placebo forshort-term treatment, the drug proved markedly superiorand a 40 mg daily dose was not much more effective than20 mg.' There then followed several controlled studieswith virtually identical design comparing omeprazole (20mg and 40 mg daily mainly and one with 60 mg) withcimetidine (400 mg four times daily) or ranitidine (150 mgtwice daily). The results were similar. Pooling the datafrom' 7 such studies and the present study (1094 patientsentered),>!' the healing rates were: at 4 weeks, OM 65%,H2RA 35%; at 8 weeks, OM 79%, H2RA 47%; and inmore severe disease, OM 62%, H2RA 15%. Completerelief of heartburn at 4 weeks occurred in 82% of patientson omeprazole compared with 44% on H2RA.

Clearly, omeprazole is remarkably effective in refluxdisease; and in all likelihood, similar results will beachieved with other proton pump blockers now beinginvestigated (such as lansoprazole). Should this com-pound now be the drug of choice in all patients witherosive oesophagitis? With time it may well become so butat present I suggest its use be restricted to patients withsevere disease. My reasons are as follows. First, the vastmajority of patients with reflux symptoms have milddisease and many have normal endoscopy; in them antacid-alginates, dietary measures, weight reduction, etc.,suffice. Second, where mild erosive disease is present,H2RAs are effective. This class of drug has a remarkablygood safety record and can be used for long-term therapyas well. Third, as yet hardly any data are available onsuitable dose, efficacy and safety of long-term omeprazolemaintenance therapy, an important consideration bearingin mind the high chance of relapse in this condition.

Today, for the short-term treatment of severe oeso-phagitis, omeprazole 20 mg to 40 mg daily for 4 to 8 weeksis the drug of choice. For long-term treatment, as yet onlyan H2RA can be used which, in my experience, is fairly

Isoproterenol tilt testing

Waxman MB, Yao L, Cameron DA, Wald RW, Roseman1. (Department of Medicine, University of Toronto andDivision of Cardiology, Toronto General Hospital,Toronto, Ontario, Canada.) Isoproterenol induction ofvaso-depressor type reaction in vaso-depressor pronepatients. Am J CardioI1989;63:58-65.

SUMMARYTo determine the usefulness of isoproterenol administration inthe diagnosis of vasovagal syncope the authors selected patientswith two or more episodes of syncope which occurred in the

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effective given in moderately high doses (cimetidine 1.6 gdaily or ranitidine 0.3 to 0.45 g daily).

Though much is yet to be established, the proton pumpblockers are likely to revolutionize the medical manage-ment of severe gastro-oesophageal reflux disease.

REFERENCESRichter JE. A critical review of current medical therapy for gastro-esophageal reflux disease. J Clin Gastroentero/1986;8 (suppll ):72-80.

2 Ottenjann R. Siewart JR. Heilmann K. Neiss A. Dopfer H. Treat-ment of reflux oesophagitis: Results of a multicentre study. In:Siewan JR. Holscher AH (eds), Diseases of the oesophagus. Munich:Springer-Verlag, 1987:1122-9.

3 Colin-Jones DG. Histamine-Z-receptor antagonists in gastro-oesophageal reflux. Gut 1989;30:1305-8.

4 Hetzel DJ. Dent J. Reed WD. et al. Healing and relapse ofsevere peptic oesophagitis after treatment with omeprazole.Gastroenterology 1988;95:903-12.

5 Zeitoun P. Desjars de Keranroue N. Isal JP. Omeprazole versusranitidine in erosive oesophagitis. LanCl.'tI987;2:621-2.

6 Bate CM. Keeling PWN. O'Morain CA. et al. Omeprazole healsreflux oesophagi tis in a greater proportion of patients thancimetidine. assessed endoscopically. histologically and symptomati-cally. Hepato·Gastroentero/1989;36:279.

7 Havelund T. Laursen LS. Skoubo-Kristensen E. et al. Omeprazoleand ranitidine in treatment of reflux oesophagitis: Double blindcomparative trial. 8r Med J 1988;296:89-92.

8 Vantrappen G. Rutgeerts L. Schurmans MD, Coenegrachts JL.Omeprazole (40 mg) is superior to ranitidine in short-term treat-ment of ulcerative reflux oesophagitis. Dig Dis Sci 1988;33:523-9.

9 Dehn TCB. Shepherd HA. Colin-Jones D. Kettlewell MGW. Doubleblind comparative study of omeprazole (40 mg od) vs cimetidine(400 mg qds) in the treatment of erosive reflux oesophagitis. Gut19!!8;29:AI440.

\0 Dammann HG. Blum AL, Lux G, et al. Unterschiedlicheheilungstendenz der reflux osophagitis nach omeprazole und ranitidin.Ergebuisse einer deutsch-osterreichisch-schweizerischen multi-zenterstudie. Disch Med Wochenschr 1986;111:123-8.

II Klinkenberg-Knol EC. Jansen JMBJ. Festen HPM. MeuwissenSGM, Lamers CBHW. Double-blind multicentre comparison ofomeprazole and ranitidine in the treatment of reflux oesophagitis.Lancet 1987;1:349-51.

K. D. BARDHAN

Rotherham, UK

erect position and which were preceded by weakness, sweating,a sensation of warmth, nausea and visual dimming. The patientswere subjected to passive tilt testing to +60° for 5 to 15minutes.No patient developed syncope with the procedure. Isoproterenolwas given in a dose of 2 fAg/minintravenously and the dose wasincreased stepwise to a maximum of 8 fAg/min.Isoproterenol wasgiven with the patient at 0° and repeated after a tilt of +60°.

Sixteen of the 48 patients developed pre-syncope or syncopeto isoproterenol tilt testing. With isoproterenol infusion, theheart rate initially increased and the mean blood pressure fell;after attaining a peak the heart rate abruptly slowed down andthis was followed by a marked decrease in arterial blood pressureand other symptoms associated with syncope. Prompt reversalof the posture caused the heart rate to increase. The greatestdecrease in heart rate occurred at 65.1±3.7 seconds and theminimal mean blood pressure occurred at 71.7±3.9 seconds.Thus, the maximum fall in heart rate preceded the maximum fall

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in blood pressure. In 4 patients, the test was repeated after giving10 mg propranolol intravenously. In these patients isoproterenoldid not cause any symptoms.

The sensitivity, specificity and positive predictive values ofthe tilt test with isoproterenol infusion were 73%,85% and 69%respectively.

COMMENTOf the many causes of syncope, vaso-depressor syncope orthe common faint is the commonest though confirmation ofits diagnosis is difficult. Upright tilt testing has beensuggested as an aid to diagnosing this condition. The overallincidence of a positive test has ranged from 6% to 13%.1.2

In normal subjects, infusion of isoproterenol does notcause bradycardia or hypotension in either the supineor 'head up' tilt position. But in individuals with vaso-depressor syncope, both the systolic blood pressure andpulse pressure decrease. Thus, the inotropic stimulation,induced by isoproterenol with the decreased ventricularvolume caused by an upright tilt, accentuates the receptorsin the heart and causes an increase in the afferent neuralactivity of the mechanoreceptors which in turn causesbradycardia and vasodilatation.

It has been shown that preceding the faint, there isincreased adrenergic activity as evidenced by an increasein heart rate, blood pressure and urinary and plasma con-centrations of epinephrine and norepinephrine.' Theincreased sympathetic activity stimulates the unmyelinatedleft ventricular vagal nerve endings (C fibres) which resultin hypotension and bradycardia. This increased adrenergicactivity suggests that if a cardioselective beta blocker is

CABO morbidity and the internalmammary artery

Berrizbeitia LO, Tessler S, Jacobonitz 11, Kaplan P,Budzilowicz L, Cunningham IN. (Departments ofSurgery and Internal Medicine, Maimonides MedicalCenter and the State University of New York HealthCenter at Brooklyn, New York, USA.) Effect ofsternotomy and coronary bypass surgery on postoperativepulmonary mechanics. Chest 1989;96:873-6.

SUMMARYFifty-five consecutive patients undergoing coronary arterybypass surgery (CAB G) were studied preoperatively and againat six to eight weeks after operation to determine the alterationin their pulmonary function. Group 1 consisted of 45 patientswho underwent sternotomy and in whom one or both internalmammary arteries (IMAs) were used as bypass conduits whilegroup 2 consisted of 10 patients who had a sternotomy andsaphenous vein grafts. Pulmonary mechanics were assessed bythe changes in FVC, FEV 1, forced expiratory flowover the middlehalf of the FVC (FEF2>-7s)and arterial blood gas determinations.

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used, the susceptibility to hypotension and bradycardiamight be prevented. This is exactly what has beendemonstrated by Goldenberg et al.4 They found that oralmetoprolol decreased or prevented these episodes over a9 month mean follow up. Thus, beta blockers may be use-ful in these patients. In the study under review only 4 ofthe 16 patients were given intravenous propranolol and,though the number is very small, in all four it amelioratedthe symptoms.

This study improves our understanding of the commonvasovagal faint. I think the following conclusions arepossible:

1. Isoproterenol testing with an upright tilt can determinethe cause of syncope. The test is simple and safe.

2. The sensitivity and specificity of this test need to befurther investigated.

3. Beta blockers may prove useful in the treatment ofvasovagal syncope.

REFERENCESShvartz E. Meyerstein N. Tilt tolerance of young men and youngwomen. Aerospace Med 1970;41:253--5.

2 Abi-Sarnra F. Maloney 10. Fonad-Tarazi FM. Castle LW. The use-fulness of head-up tilt testing and haemodynamic investigations inthe work up of syncope of unknown origin. Pace 19S5:lI: 1202-14.

3 Vingerhoets AJM. Biochemical changes in two subjects succumbingto syncope. Psychosom Med 1984;46:95-103.

4 Goldenberg IF, Almquist A. Dunbar DN. Milstein S, Pritzkar MR.Bendilt DG. Prevention of neurally mediated syncope by selectivebeta-I adrenoreceptor blockade. Circulation 1987;76 (suppl IV):A 133.

JACOB JOSEVel/ore

Patients in group 1were younger than those in group 2 (57.4±7.0compared to 69.0±4.0) and there were more males in group I.There were no statistical differences between the groups in thenumber of vessels bypassed, duration of bypass. aortic crossclamp time and cardiopulmonary fluid gradient. Patients in bothgroups experienced deterioration in pulmonary mechanics aftersurgery. However, patients in group 1had a significantly greaterreduction in FYC, FEY, and FEF2q5 compared with those ingroup 2. There was no statistically significant difference betweenpatients who had single and bilateral internal mammary grafts.The authors suggest that sternotomy and IMA harvestingcaused a decrease in postoperative pulmonary functions as dis-ruption of the sternum impaired chest wall stability and IMAremoval decreased intercostal blood supply and reduced theforce of respiration. Thus IMA harvesting might be accom-panied by a greater impairment of lung function than whensaphenous vein grafts are used.

COMMENTSince Vine berg's original description that implanting theIMA increases blood flow to the heart muscle, t.2 we havenow approached the stage where the IMA is consideredby many to be the best method for CABG. 3.4 This isbecause the procedure has not only better long termpatency rates compared to reversed saphenous vein graftsbut also better survival rates.>? In addition, patients who