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<article article-type="letter" dtd-version="1.0" specific-use="sps-1.7" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">	
	<front>
		<journal-meta>
			<journal-id journal-id-type="nlm-ta">Braz J Cardiovasc Surg</journal-id>
			<journal-id journal-id-type="publisher-id">rbccv</journal-id>
			<journal-title-group>
				<journal-title>Brazilian Journal of Cardiovascular Surgery</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Braz. J. Cardiovasc.
					Surg.</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="ppub">0102-7638</issn>
			<issn pub-type="epub">1678-9741</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cirurgia Cardiovascular</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.21470/1678-9741-2018-0302</article-id>
			<article-id pub-id-type="publisher-id">00019</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>LETTER TO THE EDITOR</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Comment on "Lidocaine and pinacidil added to blood versus crystalloid
					cardioplegic solutions: study in isolated hearts"</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Preusse</surname>
						<given-names>Claus J.</given-names>
					</name>
					<xref ref-type="aff" rid="aff1">1</xref>
					<role>MD, PhD</role>
				</contrib>
			</contrib-group>
				<aff id="aff1">
					<label>1</label>
					<institution content-type="orgname">University Bonn</institution>
					<institution content-type="orgdiv1">Department of Cardiac Surgery</institution>
					<addr-line>
        <named-content content-type="city">Bonn</named-content>
					</addr-line>
					<country country="DE">Germany</country>
					<institution content-type="original">Department of Cardiac Surgery, University
						Bonn, Bonn, Germany</institution>
				</aff>
			<pub-date pub-type="epub-ppub">
				<season>Nov-Dec</season>
				<year>2018</year>
			</pub-date>
			<volume>33</volume>
			<issue>6</issue>
			<fpage>638</fpage>
			<lpage>639</lpage>
			<permissions>
				<license license-type="open-access"
					xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an Open Access article distributed under the terms of the
						Creative Commons Attribution License, which permits unrestricted use,
						distribution, and reproduction in any medium, provided the original work is
						properly cited.</license-p>
				</license>
			</permissions>
		</article-meta>
	</front>
	<body>
		<p>In the issue 33(3) of the Brazilian Journal of Cardiovascular Surgery, Carmo et
				al.<sup>[</sup><xref ref-type="bibr" rid="B1">1</xref><sup>]</sup> published a paper
			entitled "Lidocaine and pinacidil added to blood <italic>versus</italic> crystalloid
			cardioplegic solutions: study in isolated hearts". The authors report on studies in rat
			hearts using a Langendorff model. Besides a control group, two other groups were
			investigated: Custodiol HTK solution and Del Nido solution. Pinacidil was added to both
			solutions, while lidocaine was only added to Custodiol, since Lidocaine is already an
			essential compound of Del Nido solution. After 180-min-ischemia at 4°C all hearts were
			aerobically reperfused for 90 mins and the following parameters were analyzed
			(unfortunately only as percentage of recovery): contractility, coronary resistance and
			alpha-fodrin degeneration.</p>
		<p>The authors reported on superior outcome by Del Nido solution after
			90-min-reperfusion.</p>
		<p>Although the study shows some interesting approaches to intraoperative myocardial
			protection, some aspects are objectionable regarding their comparative analytical
			methodology.</p>
		<p>First, only one compound - pinacidil - was added to Del Nido solution, while two,
			pinacidil and lidocaine, were added to custodiol, since lidocaine is already an
			essential component of Del Nido solution. This is not consistent with a clean,
			scientifically acceptable comparative analysis, as Del Nido already meets one of the
			parameters subject to the investigation.</p>
		<p>Second, to measure myocardial contractility, mostly dP/dt max. is used in appropriate
			experimental or clinical investigations. However, from scientific point of view this is
			not completely accurate, since the time until the maximal pressure is reached, may play
			an important role. Therefore, it would be correct to additionally divide dP/dt by t
			(time).</p>
		<p>Third, Custodiol is the only highly buffered cardioplegic solution available worldwide.
			The efficacy of buffers in any cardioplegic solution can be clearly demonstrated by
			simultaneous measurements of extracellular myocardial pH and of myocardial lactate
			content during ischemia<sup>[</sup><xref ref-type="bibr" rid="B2">2</xref><sup>]</sup>.
			Lactate/pH relationships differ depending on the cardioplegic solutions applied and
			concerning a buffered solution, the lactate/pH relationship depends on the nature of the
			buffer applied, on buffer concentration and, on additional compounds in a cardioplegic
				solution<sup>[</sup><xref ref-type="bibr" rid="B3">3</xref><sup>]</sup>. Any drug
			that stabilizes myocardial membranes, will impair the permeation of H<sup>+</sup>-ions
			from the intra- to the extracellular space. Such impaired permeation leads to an
			intracellular 'overload' of H<sup>+</sup>-ions and, conversely, to less acidification of
			the myocardial extracellular space. Consequently, the lactate/pH curve will shift
			towards alkalosis! This effect should occur if procaine or lidocaine are parts of the
			solution, since both drugs are membrane stabilizing drugs. In experiments on ischemic
			hearts of mongrel dogs at 15°C we compared histidine buffered solutions with and without
			procaine (<xref ref-type="fig" rid="f1">Figure 1</xref>). In this experiment we were
			able to demonstrate the aforementioned effect on the extracellular pH. Although both
			solutions contained equal buffer capacities, the extracellular pH is more alkalotic in
			the procaine group. This means that the total available extracellular buffering capacity
			is not effectively utilized, <italic>i.e</italic>. one of the principal benefits of the
			solution - its buffering capacity - is not sufficiently realized<sup>[</sup><xref
				ref-type="bibr" rid="B4">4</xref><sup>]</sup>. Therefore, it is not surprising that
			the custodiol-LP group led to inferior results.</p>
		<p>
			<fig id="f1">
				<label>Fig. 1</label>
				<caption>
					<title>Experiments were performed on ischemic mongrel dog hearts at 15°C. For
						myocardial protection Custodiol solution with or without procaine was used.
						(Methods see also Preusse et al.<sup>[</sup><xref ref-type="bibr" rid="B2"
							>2</xref><sup>]</sup>)</title>
				</caption>
				<graphic xlink:href="0102-7638-rbccv-33-06-0638-gf01.jpg"/>
			</fig>
		</p>
		<p>The results of the current study differ from an experimental study in South Korea in 2003
			which was also performed on rat hearts (!) being protected either by original custodiol
			or by Del Nido solution. It became obvious that after two-hour-arrest mitochondrial
			scoring was superior in the custodiol group<sup>[</sup><xref ref-type="bibr" rid="B5"
				>5</xref><sup>]</sup>.</p>
		<p>Given the aforementioned objections, we would question the conclusions drawn by the
			authors. They would have been correct, had they concluded that a decisively modified (!)
			Custodiol solution - mainly by lidocaine - causes inferior efficacy in myocardial
			protection due to the relatively reduced buffering power. But their study does not
			address the intraoperative protective efficacy of the original version of custodiol and
			therefore, the results are not applicable to clinical usage. In conclusion, this paper
			does not represent a valid comparative study between custodiol and Del Nido
			solutions.</p>
	</body>
	<back>
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</article>
